Use Of Chemotherapeutic Agents

ABSTRACT

The use of chemotherapeutic agents for the preparation of a medicament for the topical and/or local treatment of diseases caused by bacteria and/or for prophylaxis in humans or animals.

The present invention relates to the use of chemotherapeutic agents forthe preparation of a medicament for the topical and/or local treatmentof diseases caused by bacteria and/or for prophylaxis in humans oranimals.

Bacteria can be the cause of a large number of diseases and can moreoverimpair wound healing. In the oral region, for example, tooth decay(caries) is caused by microbes specific to the mouth. Oral bacteriaconvert dietary carbohydrates to acids capable of dissolving the toothenamel (enamelum) and dentin (dentinum). If the enamel surface isbroken, the bacteria penetrate further into the underlying dentin. Theradial dentinal tubules contain pulp processes, so partial or totalinfection and hence inflammation of the pulp occurs as the situationdevelops. The effect of inflammation of the pulp is to increase thecongestion of blood. As the pulp is located in the rigid pulp cavity, itcannot expand and pain occurs. If the situation is left untreated, theconsequences are necrosis of the pulp tissue and bacterial decomposition(gangrene). If the gangrenous matter is not removed, this is followed byinflammations outside the root tip. Granulomas, cysts, fistulation orabscesses may develop. Gas formation also exacerbates the pain at thisstage.

Inflammation of the periodontium also involves bacteria. Theperiodontium consists of the gingiva, the annular ligament of theradius, the periodontal membrane and the intermediate Sharpey's fibres.An inflammation, periodontitis, can affect individual regions or theentire periodontium. Periodontitis, like caries, is caused by dentalplaque at the margins of the gingiva, which hardens to tartar due tocalcareous infiltrations. Bacteria living in the plaque form metabolicproducts which cause periodontal disease. The gingiva gradually recedesand the periodontal membrane and alveolar bone begin to disintegrate.Sites of infection form in the surrounding tissue. The consequences arecontinued destruction of the bones and loosening of the teeth, whichultimately fall out. Damage in the oral region can also lead to diseasesin other body organs.

Calcium hydroxide preparations or zinc oxide/clove oil (eugenol) areused for the treatment of caries profunda, both in the case of exposedpulp and when the dentin covering is still unbroken. An infected andnecrotized pulp is removed as far as possible and the pulp cavity isfilled with suitable root fillers. If the pulp is gangrenous, successcan only be expected if the contaminated root canal system and thedentin near the canal can be disinfected. The main problems are theinaccessibility of the bacterially infected apical delta of the rootcanals, which is difficult to clean, and also the infected canal wallsystem, which has to be removed with considerable effort usinginstruments. A gangrene treatment is therefore normally a compromisesolution and is wholly rejected by some schools. In principle,contraindications for a gangrene treatment are multirooted teeth andapical processes visible by X-ray. Extraction of the tooth is indicatedin these cases. Periodontal diseases are treated by the removal ofsubgingival concrements. Other treatments use medicaments such ascaustic agents, anti-inflammatories or vitamins.

Infections in the oral region are treated using antibiotics andchemotherapeutic agents with an antibacterial action, although theseshould only be administered after critical diagnosis. The preferredagents are antibiotics such as penicillin G or oral penicillins.Possible alternatives are erythromycin, lincomycin, clindamycin and, ifappropriate, sulfonamides. The preferred agents in the case of mixedinfections with Gram-negative microbes are broad-spectrum penicillinssuch as ampicillin, which can optionally be replaced by tetracyclines.Antibiotics and chemotherapeutic agents are always administeredsystemically. According to the prevailing school of thought, agents usedfor systemic chemotherapy should not be used as local antibiotics.

The current use of antimicrobial substances in dental medicine isdescribed by B. M. Owens and N. J. Schuman (Journal of ClinicalPediatric Dentistry, 1994 (Winter), 18, 129-134; cited in Medline, AN94331337). According to these authors, there are two distinct categoriesof antimicrobial substances, namely naturally occurring substances fromfungi (penicillins and cephalosporins), bacteria and actinomycetes(aminoglycosides), and their derivatives, which are called antibiotics,and compounds of synthetic origin (sulfanilamides and quinolones), whichare called chemotherapeutic agents. The group of antibiotics which areimportant for dental medicine are penicillins, cephalosporins andaminoglycosides, as well as erythromycin. Because of their goodefficacy, low costs and ease of use, these antibiotics are the preferredagents for many if not most odontogenous infections. The substances ofsynthetic origin are less valuable in dental medicine. According to theprevailing school of thought, they are frequently characterized by highcosts, lack of efficacy and toxicity for the patient.

The sensitivity to antimicrobial agents of microbes which causeprogressive periodontitis or odontogenous abscesses has been studied invitro by S. Eick et al. (Int. J. Antimicrob. Agents, 1999, 12, 41-46)using modern antibiotics and chemotherapeutic agents, i.e. penicillin,amoxicillin, cefoxitin, clindamycin, doxycycline, metronidazole andciprofloxacin. The result was to recommend clindamycin for antimicrobialtreatments.

Antibiotics have been used in dental medicine both systemically andtopically to treat patients. U. Wahlmann et al. (Int. J. Antimicrob.Agents, 1999, 12, 253-256) have reported the effects of the systemicadministration of cefuroxim ten minutes prior to a dental extraction.Bacteraemia occurred with a lower frequency in the group treated withcefuroxim than in the untreated group.

K. Kosowska and P. B. Heczko (Med. Dosw. Mikrobiol., 1977, 29, 101-106;cited in Chemical Abstracts, CA 88:69315) have reported the topical useof a variety of antibiotics. They treated infected teeth with variousantibiotics, namely erythromycin, neomycin, chloramphenicol, colistin,nystatin or dexamethasone. The aerobic flora in the root canals waseliminated in about 55% of cases. However, the antibiotic resistance ofthe microorganisms isolated from the root canals after the treatment hadbeen increased by the treatment. The resistance of Staphylococcusepidermis to erythromycin or methicillin was increased three-fold ortwo-fold. The majority of Staphylococcus aureus strains were resistantto erythromycin, chloramphenicol and penicillin.

The authors of the above literature references are all in agreement thatthe topical use of antibiotics and chemotherapeutic agents administeredas sucking tablets, throat tablets, lozenges, styli, cones, powders orointments are only of very little importance because of the frequentoccurrence of increased resistance of the pathogens and because of thehigh sensitization rate. The therapeutic benefit is generally alsolimited in wounds with adequate external drainage. The substances usedare scarcely absorbed, if at all, so their action cannot be expected topenetrate deeper into the tissue.

Accordingly, given the current state of the art in human and veterinarydental medicine, there is a great need for agents which have a highactivity against the microbes occurring in the region of the mouth,teeth and jaws or in oral wounds, have a rapid bactericidal action, havea good local tolerability, elicit a low tendency to generate antibioticresistance, can be applied topically and/or locally and hence are easyto administer, place a minimum systemic burden on the organism whenadministered topically/locally, and have a good tissue penetration, andwhose use ensures the preservation of the damaged teeth.

Bacteria are also important in wound care. Wounds are tissue defects onthe body surface and can be caused by injuries, operations, infectionsor pathophysiological processes. Wounds are dangerous inter alia becauseof possible infections due to penetration by pathogenic bacteria.Bacterial colonization of the wound can slow down or prevent the healingprocess or lead to other complications such as lymphangitis, sepsis orchronic infections.

Infected wounds must receive an antimicrobial treatment to controlpathogenic microbes. Moreover, in a similar way to necrotic wounds, thewound must be cleaned to remove foreign bodies and cell detritus so thatit can progress to the next healing phase. The treatment of an infectedwound normally consists of a combined systemic and local approach whereoptionally antibiotics are used and a suitable dressing is applied whichmay itself have an antibacterial action. In many cases wound infectionscan be successfully treated by the administration of systemically activeantibiotics, but the systemic administration of an antibioticnecessarily burdens the entire organism. This may be contraindicated inmany cases, for example due to the patient's clinical situation, if thepatient has primary diseases or if an allergizing potential exists. Itis advantageous in such cases to apply the antibiotic topically and/orlocally so that it can also be used in a higher local tissueconcentration. Topical/local applications may also be favoured by otherfactors, as in the case of certain hospital epidemiologies, or economicaspects such as the amounts needed, the prices of the medicaments andthe costs due to side effects. However, the use of topical antibioticsis not generally recommended because this can lead to allergic reactionsor to the formation of antibiotic-resistant species of bacteria. It istherefore regarded as particularly important to limit the use of topicalantibiotics.

Nowadays a local antibiotic treatment is used only for superficial skininfections because the antibiotic can act directly on the pathogens. Alocal application is unsuccessful in the case of deep skin infectionsbecause the antibiotics do not penetrate the intact skin. There arethree preferred groups of local antibiotics in use today. These arepolypeptides such as bacitracin, tyrothricin, colistin and polymyxin B,or aminoglycosides such as neomycin, kanamycin and paromycin ormupirocin. However, with the presence of local or systemic toxicity andthe danger of the secondary development of bacterial resistance, localantibiotics should only be used with great restraint. In local therapieswith gyrase inhibitors, incorporation into plastic materials has beenproposed as a possible clinical application in addition to conventionalforms of administration such as eye drops, ear drops, instillationsolutions, powders and healing ointments (W. Stille, Fortschritte derantimikrobiellen und antineoplastischen Chemotherapie (Advances inantimicrobial and antineoplastic chemotherapy), vol. 6-10, 1987, pp.1575-1583).

Accordingly, given the current state of the art, there is also a need inhuman and veterinary medicine for topically and/or locally applicableagents with an antibiotic action which have a high activity against themicrobes occurring in wounds, have a rapid bactericidal action, have agood local tolerability, elicit a low tendency to generate antibioticresistance, are easy to administer by topical and/or local application,place a minimum systemic burden on the organism when administeredtopically/locally, have a good tissue penetration, are also suitable forthe treatment of deep infections and additionally accelerate the woundhealing process.

It has now been found, surprisingly, that certain chemotherapeuticagents, administered locally and/or topically, have an extremelypositive effect in a variety of ways on the treatment of diseases causedby bacteria in the oral region of humans and animals, for example dentaland periodontal diseases, and on wound healing. Medicaments whichcontain these chemotherapeutic agents can be used successfully in dentalmedicine against microbes encountered in the soft tissue and/or hardtissue, where they lead to inflammations. The medicaments are generallysuitable for the local treatment of endodontal syndromes such aspulpitis due to carious diseases, for the prophylaxis of dentin wounds,for the topical treatment of the infected root canal and the periapicaltissue, and also for the topical treatment of periodontal diseases, ofosseomucosal wounds with disturbed wound healing, for example afterdental extraction, and of soft tissue infections. Such diseases arecaused by bacteria in the hard dental tissue, for example in the case ofinfections in the crown and root dentin, in the dentin inside the rootcanal and in the root cement in the apical region of the root of thetooth. Also included are bacterial infections of the jawbone andalveolar bone. They are also to be understood as including infections inthe soft tissues, for instance in the pulp, in the periodontal tissue,in the gingival mucosa, in the alveolar mucosa, in the labial and buccalmucosa, in the palatine mucosa and in the periglottis. It has furtherbeen found, surprisingly, that the use of these chemotherapeutic agentsin human and veterinary medicine also has a positive effect in a varietyof ways on the treatment and prophylaxis of wounds. This was shown inthe treatment of different forms of wounds, for example in surgicalinfections such as postoperative or posttraumatic wound infections, inperioperative prophylaxis, in infected burns, in hand infections, inpostoperative sepsis, in infected ulcers and gangrenes and in skininfections such as acute and chronic bacterial skin infections,secondarily infected dermatoses or acne and rosacea. These lists areexamples and do not imply a limitation to the areas mentioned.

These diseases can be treated according to the invention by the localand/or topical application of chemotherapeutic agents.

In terms of the invention, chemotherapeutic agents are derivatives ofquinolone-carboxylic acid or naphthyridonecarboxylic acid of generalformula (I):

in which:

-   -   A is CH, C-halogen, C—CH₃, C—CN, C—OCH₃, C—OCHF₂ or N,    -   R1 is C₁-C₅-alkyl, C₁-C₅-alkenyl, 2-fluoroethyl, cycloalkyl,        bicycloalkyl, 2-fluorocyclopropyl, 1-oxetan-3-yl, methylamino,        optionally substituted phenyl or pyridyl, or A and R1 together        form the group C—O—CH₂—CH(CH₃)—,    -   R2 is hydrogen or C₁-C₃-alkyl optionally substituted by        hydroxyl, halogen or amino,    -   R3 is hydrogen, halogen, methyl, amino or NH—NH₂,    -   R4 is hydrogen, halogen or amino, and    -   R5 is an optionally monosubstituted or polysubstituted mono-,        bi- or tricyclic alicycle which is saturated or has at least one        double bond and which optionally has at least one heteroatom in        the ring system, or an aromatic mono-, bi- or tricycle        optionally having at least one heteroatom,        and/or 4H-4-oxoquinolizines of general formula (II):        in which:    -   R1 is hydrogen or C₁-C₃-alkyl, and    -   R2 is an optionally monosubstituted or polysubstituted mono-,        bi- or tricyclic alicycle which is saturated or has at least one        double bond and which optionally has at least one heteroatom in        the ring system, or an aromatic mono-, bi- or tricycle        optionally having at least one heteroatom,        and/or their corresponding hydrates and/or their corresponding        physiologically compatible acid addition salts and/or optionally        the corresponding physiologically compatible salts of the        carboxylic acids on which they are based, i.e. the compounds of        general formula (I) in which R2 is H and/or the compounds of        general formula (II) in which R1 is H, and/or corresponding        enantiomers and/or corresponding diastereomers and/or        corresponding racemates and/or corresponding mixtures of at        least two of the above-mentioned compounds.

When administered topically and/or locally, these compounds have abeneficial action in the treatment of diseases caused by bacteria in theoral region of humans and animals, especially in the treatment ofpulpitis, including infections of the root canal and the periapicaltissue, periodontal diseases and odontogenous or oral soft tissueinfections, in the prophylaxis of dentin wounds, in the treatment offorms of wounds in humans and animals arising from surgical infectionssuch as postoperative or posttraumatic wound infections, inperioperative prophylaxis, in infected burns, in hand infections, inpostoperative sepsis, in infected ulcers and gangrenes, in acute andchronic bacterial skin infections, secondarily infected dermatoses oracne and rosacea, and in general for the acceleration of wound healingin humans and animals.

It is preferred to use at least one of these compounds to prepare apharmaceutical product, especially a medicament, for the topical and/orlocal treatment of diseases caused by bacteria or for the accelerationof wound healing.

It is preferred to use the compounds of formula (I) in which

-   -   A is CH, CF, CCl, CBr, C—CH₃, C—CN, C—OCH₃, C—OCHF₂ or N,    -   R1 is ethyl, 1,1-dimethylethyl, 1-ethenyl,        1,1-dimethylprop-2-ynyl, 2-fluoroethyl, cyclopropyl,        bicyclo(1.1.1)pent-1-yl, 2-fluorocyclopropyl, 1-oxetan-3-yl,        methylamino, 4-fluorophenyl, 2,4-difluorophenyl,        5-amino-2,4-difluorophenyl, 5-fluoropyridin-2-yl or        6-amino-3,5-difluoropyridin-2-yl, or A and R1 together form the        group C—O—CH₂—CH(CH₃)—, the —CH(CH₃)-part of this group being        bonded to the nitrogen atom of the heterocycle,    -   R2 is hydrogen, methyl or ethyl,    -   R3 is hydrogen, F, Cl, Br, methyl, amino or NH—NH₂,    -   R4 is hydrogen, F or amino, and    -   R5 is optionally monosubstituted or polysubstituted cyclopropyl,        azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl,        phenyl, pyrrolyl, pyridyl or imidazolyl, it optionally also        being possible for at least two substituents to be coupled        together,        and/or the compounds of formula (II) in which    -   R1 is hydrogen, and    -   R2 is optionally monosubstituted or polysubstituted cyclopropyl,        azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl or        morpholinyl, it optionally also being possible for at least two        substituents to be coupled together.

It is particularly preferred to use the compounds of formula (I) inwhich

-   -   A is CH, CF, CCl, C—CN, C—OCH₃ or N,    -   R1 is cyclopropyl, 2-fluorocyclopropyl, 4-fluorophenyl or        2,4-difluorophenyl, or A and R1 together form the group        C—O—CH₂—CH(CH₃)—, the —CH(CH₃)-part of this group being bonded        to the nitrogen atom of the heterocycle,    -   R2 is hydrogen,    -   R3 is hydrogen or amino,    -   R4 is hydrogen or F, and    -   R5 is optionally monosubstituted or polysubstituted        pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl, it        optionally also being possible for at least two substituents to        be coupled together.

It is very particularly preferred to use the compounds of formula (I) inwhich

-   -   A is CH, CF, CCl, C—OCH₃ or N,    -   R1 is cyclopropyl or 2,4-difluorophenyl, or A and R1 together        form the group C—O—CH₂—CH(CH₃)—, the CH(CH₃)-part of this group        being bonded to the nitrogen atom of the heterocycle,    -   R2 is hydrogen,    -   R3 is hydrogen or amino,    -   R4 is hydrogen or F, and    -   R5 is pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl or        3-aza-bicyclo(3.1.0)hexyl optionally substituted by amino,        methyl, amino-methyl and/or methoxyimino, or        piperidinopyrrolidinyl.

Bi- or tricyclic alicycles or aromatic bi- or tricycles R5 in generalformula (I) and R2 in general formula (II) are also understood asincluding fused ring systems which can optionally have at least onedouble bond and/or at least one heteroatom in the ring system.

Examples of radicals R5 in the compounds of formula (I) are1-aminocyclopropyl, 3-hydroxyazetidin-1-yl, 3-aminoazetidin-1-yl,3-methylaminoazetidin-1-yl, 3-amino-2-methylazetidin-1-yl,3-amino-3-methylazetidin-1-yl, 3-amino-2,3-dimethylazetidin-1-yl,3-aminopyrrolidin-1-yl, 3-(2-amino-1-oxopropyl)amino-1-pyrrolidin-1-yl,3-norvalylnorvalylamino-1-pyrrolidin-1-yl,3-amino-3-fluoromethylpyrrolidin-1-yl, 3-amino-4-methylpyrrolidin-1-yl,3-amino-4-fluoromethylpyrrolidin-1-yl, 4-amino-2-methylpyrrolidin-1-yl,4-amino-3,3-dimethyl-1-pyrrolidin-1-yl, 3-amino-3-phenylpyrrolidin-1-yl,3-amino-4-cyclopropylpyrrolidin-1-yl, 3-aminomethylpyrrolidin-1-yl,3-ethylaminomethylpyrrolidin-1-yl, 3-(1-aminoethyl)-1-pyrrolidin-1-yl,3-(1-amino-1-methylethyl)pyrrolidin-1-yl,3-aminomethyl-3-methylpyrrolidin-1-yl,3-aminomethyl-3-fluoromethylpyrrolidin-1-yl,3-aminomethyl-4-methylpyrrolidin-1-yl,3-aminomethyl-4-trifluoromethylpyrrolidin-1-yl,3-aminomethyl-4-chloropyrrolidin-1-yl,3-aminomethyl-4-methoxyiminopyrrolidin-1-yl,3-(2-methyl-1H-imidazol-1-yl)pyrrolidin-1-yl,3-(4-methyl-1,2,3-triazol-1-yl)pyrrolidin-1-yl,3-methylaminopiperidin-1-yl, 4-hydroxypiperidin-1-yl,4-hydroxyiminopiperidin-1-yl, piperazin-1-yl, 3-methyl-1-piperazinyl,4-methylpiperazin-1-yl, 4-ethylpiperazin-1-yl, 4-acetylpiperazin-1-yl,4-(5-methyl-2-oxo-1,3-dioxol-4-yl)methylpiperazin-1-yl,4-(3-carboxy-1-oxopropyl)piperazin-1-yl, 3,5-dimethylpiperazin-1-yl,2,4,5-trimethylpiperazin-1-yl, 3,4,5-trimethylpiperazin-1-yl,2-aminomethylmorpholin-4-yl, 2-dimethylaminomethylmorpholin-4-yl,3-methylaminomethylmorpholin-4-yl, 7-amino-5-azaspiro(2.4)heptan-5-yl,8-amino-6-azaspiro(3.4)octan-6-yl,6-amino-3-azabicyclo(3.1.0)hexan-3-yl,6-alanylalanylamino-3-azabicyclo(3.1.0)hexan-3-yl,6-amino-1-methyl-3-azabicyclo(3.2.0)heptan-3-yl,6-methyl-2,5-diazabicyclo(2.2.1)-heptan-2-yl,2,5-diazabicyclo(2.2.1)heptan-2-yl,8-methyl-3,8-diazabicyclo(3.2.1)-octan-3-yl,5-amino-2-aza-2-spiro[4.4]nonyl,1-aminomethyl-8-aza-8-bicyclo-[4.3.0]nonyl,5-aminomethyl-7-aza-2-oxo-7-bicyclo[3.3.0]octyl,1-aminomethyl-7-aza-3-oxo-7-bicyclo[3.3.0]octyl,2,7-diaza-7-bicyclo[3.3.0]octyl, 3,7-diaza-3-bicyclo[3.3.0]octyl,2,8-diaza-8-bicyclo[4.3.0]nonyl, 5,8-diaza-2-oxo-8-bicyclo-[4.3.0]nonyl,3,8-diaza-8-bicyclo[4.3.0]nonyl, 2,7-diaza-7-bicyclo[4.3.0]nonyl,3,9-diaza-9-bicyclo[4.3.0]nonyl, 3,9-diaza-3-bicyclo[4.3.0]nonyl,7-amino-3-aza-3-bicyclo[4.1.0]heptyl, 7-amino-5-azaspiro[2.4]hept-5-ylor 7-methylamino-5-azaspiro[2.4]hept-5-yl,2,7-diaza-2-bicyclo[3.3.0]octyl, 4-amino-1,3-dihydro-2H-isoindol-2-yl,3,4-dihydro-2(1H)-isoquinolinyl, hexahydropyrrolo[3,4-b]pyrrol-5(1H)-yl,octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl,hexahydropyrrolo[3,4-b]-1,4-oxazin-6(2H)-yl,2,3-dihydro-1-methyl-1H-isoindol-5-yl, pyridin-4-yl,2,6-dimethylpyridin-4-yl, 1H-pyrrol-1-yl or 1H-imidazol-1-yl.

Examples of radicals R2 in the compounds of formula (II) areazetidin-1-yl, 2-hydroxymethylazetidin-1-yl, 2-aminomethylazetidin-1-yl,pyrrolidin-1-yl, isoxazolin-1-yl, 2-methylpyrazolidin-1-yl,3-hydroxypyrrolidin-1-yl, 3-carboxypyrrolidin-1-yl,3-aminopyrrolidin-1-yl, 3-aminomethylpyrrolidin-1-yl,3-methylaminopyrrolidin-1-yl, 3-ethylaminopyrrolidin-1-yl,3-fluoroethylaminopyrrolidin-1-yl, 3-trifluoroethylaminopyrrolidin-1-yl,3-methoxyethylaminopyrrolidin-1-yl,3-(N-methyl-N-cyclo-propylamino)pyrrolidin-1-yl,3-amino-4-cyclopropylpyrrolidin-1-yl,4-methyl-3-methylaminopyrrolidin-1-yl,3-cyclopropylamino-4-methylpyrrolidin-1-yl,3-(1-amino-8-aza-8-bicyclo[4.3.0]nonyl, 3-aminomethylpyrrolidin-1-yl,3-aminomethyl-3-trifluoromethylpyrrolidin-1-yl,5-amino-2-aza-2-spiro[4.4]nonyl,1-aminomethyl-8-aza-8-bicyclo[4.3.0]nonyl,5-aminomethyl-7-aza-2-oxo-7-bicyclo[3.3.0]octyl,1-aminomethyl-7-aza-3-oxo-7-bicyclo[3.3.0]octyl,2,7-diaza-7-bicyclo[3.3.0]octyl, 3,7-diaza-3-bicyclo[3.3.0]octyl,2,8-diaza-8-bicyclo[4.3.0]nonyl, 5,8-diaza-2-oxo-8-bicyclo[4.3.0]nonyl,3,8-diaza-8-bicyclo[4.3.0]nonyl, 2,7-diaza-7-bicyclo[4.3.0]nonyl,3,9-diaza-9-bicyclo[4.3.0]nonyl, 2,7-diaza-2-bicyclo[3.3.0]octyl,piperidin-1-yl, 3-aminopiperidin-1-yl, 3-amino-4-methylpiperidin-1-yl,3,9-diaza-3-bicyclo[4.3.0]nonyl, 7-amino-3-aza-3-bicyclo[4.1.0]heptyl,7-amino-5-azaspiro[2.4]hept-5-yl or7-methylamino-5-azaspiro[2.4]hept-5-yl.

Examples of compounds of formula (I) or formula (II) are1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-[3-(methylamino)-1-piperidinyl]-4-oxo-3-quinolinecarboxylicacid (balofloxacin),8-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-7-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]-4-oxo-3-quinolinecarboxylicacid monohydrochloride (BAY Y3118),1-cyclopropyl-6-fluoro-8-difluoromethoxy-1,4-dihydro-7-((3S)-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylicacid hydrochloride (caderofloxacin),1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylicacid (ciprofloxacin),7-(3-amino-1-pyrrolidinyl)-8-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid (clinafloxacin),(1α,5α,6β)-(+)-7-(6-amino-1-methyl-3-azabicyclo[3.2.0]hept-3-yl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylicacid (ecenofloxacin),1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-1,8-naphthyridine-3-carboxylicacid (enoxacin),1-cyclopropyl-7-(4-ethyl-1-piperazinyl)-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid (enrofloxacin),6-fluoro-1-(5-fluoro-2-pyridinyl)-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylicacid (fandofloxacin),6,8-difluoro-1-(2-fluoroethyl)-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylicacid (fleroxacin),1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(3-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylicacid (gatifloxacin),7-[(4Z)-3-(aminomethyl)-4-(methoxyimino)-1-pyrrolidinyl]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylicacid (gemifloxacin),1-cyclopropyl-6-fluoro-1,4-dihydro-5-methyl-7-(3-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylicacid (grepafloxacin),(3S)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylicacid (levofloxacin),1-ethyl-6,8-difluoro-1,4-dihydro-7-(3-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylicacid (lomefloxacin),1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]-4-oxo-3-quinolinecarboxylicacid (moxifloxacin),9-fluoro-6,7-dihydro-8-(4-hydroxy-1-piperidinyl)-5-methyl-1-oxo-1H,5H-benzo[ij]quinolizine-2-carboxylicacid (nadifloxacin),1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylicacid (norfloxacin),9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylicacid (ofloxacin),5-amino-7-[(7S)-7-amino-5-azaspiro[2.4]hept-5-yl]-1-cyclopropyl-6-fluoro-1,4-dihydro-8-methyl-4-oxo-3-quinolinecarboxylicacid (olamufloxacin),(3S)-10-(1-aminocyclopropyl)-9-fluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylicacid (pazufloxacin),1-ethyl-6-fluoro-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylicacid (pefloxacin),6-fluoro-1-methyl-7-[4-[(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl]-1-piperazinyl]-4-oxo-1H,4H-[1,3]thiazeto[3,2-a]quinoline-3-carboxylicacid (prulifloxacin),1-ethyl-1,4-dihydro-4-oxo-7-(4-pyridinyl)-3-quinoline-carboxylic acid(rosoxacin),7-[(7S)-7-amino-5-azaspiro[2.4]hept-5-yl]-8-chloro-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl]-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid (sitafloxacin),5-amino-1-cyclopropyl-7-[(3R,5S)-3,5-dimethyl-1-piperazinyl]-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid (sparfloxacin),7-(3-amino-1-pyrrolidinyl)-1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylicacid (tosufloxacin) or7-(1α,5α,6α-6-amino-3-azabicyclo[3.1.0]hex-3-yl)-1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylicacid (trovafloxacin).

If corresponding physiologically compatible acid addition salts of thecompounds of general formula (I) and/or of general formula (II) areused, these can preferably be selected from the group comprisinghydrochloride, hydrobromide, methanesulfonate and toluenesulfonate. Ifcorresponding physiologically compatible salts of the carboxylic acidson which said compounds are based are used, these can preferably beselected from the group comprising alkali metal salts, alkaline earthmetal salts, ammonium salts, guanidinium salts and silver salts. It isalso possible to use mixtures of at least two of the above-mentionedphysiologically compatible salts.

The above-mentioned compounds of formula (I) or formula (II) are knownand can be prepared by conventional processes familiar to those skilledin the art. It is also known that the compounds of formula (I) orformula (II) have an antibiotic action and have an antibacterialspectrum against Gram-positive and Gram-negative microbes. It is alsoknown that it is possible to use the compounds of formula (I) or formula(II) for the systemic treatment of diseases which can be caused byGram-negative, Gram-positive or bacterioid microorganisms. It is alsoknown that ciprofloxacin can be used in topical form in ophthalmology.

The compounds of general formula (I) or of general formula (II) can beused for the topical and/or local treatment of a variety of diseasescaused by bacteria and for prophylaxis in humans and animals.

The compounds of formula (I) or formula (II) can be used particularly indental medicine and/or for improving wound healing in general medicineor veterinary medicine. The uses according to the invention of thecompounds of formula (I) or formula (II) preferably involve a)endodontal treatments such as the topical treatment of pulpitis due tocarious diseases, the prophylaxis of dentin wounds or the topicaltreatment of the infected root canal and the periapical region, b) thetopical treatment of periodontal diseases, c) the topical treatment oforal osseomucosal wounds with disturbed wound healing, or prophylactictreatment, for example after extractions, cystectomy or incisions duee.g. to phlegmons or parulides, d) the topical and/or local treatment ofpostoperative or posttraumatic wound infections, e) perioperativeprophylaxis, f) infected burns, g) hand infections, h) postoperativesepsis, i) infected ulcers and gangrenes, j) acute and chronic bacterialskin infections, k) secondarily infected dermatoses, l) acne androsacea, or m) mucosal ulcerations.

Preferred uses according to the invention are described below using theareas of dental medicine and wound healing as examples.

Topical Treatment of Pulpitis Due to Carious Diseases

The particular problems associated with treatment of the pulp are thesmall lymph supply, its position as a terminal organ with a smallcollateral circulation, and the influence of external stimuli given itslocation in a rigid, inflexible cavity. In the case of carious defects,the microorganisms advance in the direction of the pulp, cross theenamel-dentin interface and soften the dentin cone. If the cariousprocess reaches half of the total dentin layer, the pulp is alreadyhistologically modified, even though clinical symptoms are often stillabsent. If the caries advances further without penetrating the remainderof the dentin covering, symptoms of pulpitis are normally experienced.If the caries reaches the pulp, different histopathological forms arise.These consequences of the carious process are attributable to the factthat dentin has radial channels, called dentinal tubules, runningthrough it, said tubules containing pulp processes. These processes ofthe dentinogenic cells (odontoblasts), which are located at theperiphery of the pulp, serve inter alia to conduct stimuli. It is knownthat the microorganisms and their toxins follow the dentinal tubules. Ifthe caries extensively penetrates the dentin layer or reaches the pulp,the condition is referred to as caries profunda.

The particular problem associated with the diagnosis of a pulp diseaseis that the histological and clinical pictures are often quitedifferent. As pain is sensed and interpreted differently by differentpatients, there is always the risk of a false diagnosis. The pulpinfection has often progressed further than is clinically ascertainable.Under the conventional treatment, there is then the danger of residualmicrobes being left behind.

In the conventional treatment of caries normally used today, the cariousmatter is first removed. Then the cavity is disinfected, for examplewith hydrogen peroxide, and, depending on the degree of pulpinflammation, is indirectly or directly capped. This means that a thinresidual dentin covering is left untouched or the exposed pulp is coatedwith a medicament. This is done using either calcium hydroxide or zincoxide/eugenol. Both medicaments are strongly alkaline, have anantibacterial action and induce caustic necrosis in a local region ofthe pulp. This has the effect of building secondary dentin, depending onthe extent of the previous damage and the resistance situation. Thecapping agent is covered with a reliner, for example zinc phosphatecement. In the same session or at a later time, the definitive fillingis prepared, for example with a composite cement. In cases of particularpain symptoms or where the pulp no longer reacts to external stimuli, itis assumed that the pulp can no longer regenerate or that it is dead. Inthese cases the pulp is removed and a root treatment is carried out.

The topical treatment of infected dentin and pulpitis with antibioticshas hitherto been described in the scientific literature asunsuccessful. As the main argument against this method of treatment, itis stated that the microbes in question (anaerobes and aerobes) wereonly dealt with to a very limited extent by the antibiotics tested. Itwas further established that the antibiotics tested earlier for theseindications generally have only a bacteriostatic action and not abactericidal action. This allows resistant microbes to get out ofcontrol and hypersensitivity reactions against a particular antibioticcan be triggered.

It has now been found, surprisingly, that, when applied topically and/orlocally to the periodontal interstice in dentistry, the antibiotics offormula (I) or formula (II) completely control the bacteria occurring inodontogenous infections, and additionally that the disadvantages of theconventional treatment described above do not arise. It has further beenfound that the compounds of formula (I) or formula (II) have a hightissue penetration in the odontogenous region. It has also been foundthat, under treatment with the compounds of formula (I) or formula (II),the microbes of odontogenous infections have no tendency to developresistance. This is of great importance because, for example in the caseof caries profunda, it is always necessary to decide whether softenedresidual dentin can be left over the pulp. By virtue of completeelimination of the microbes present, there is now a novel method oftreatment wherein a thin softened dentin covering can be left if thecompounds of formula (I) or formula (II) are used. This method oftreatment makes it possible to free infected dentin layers of microbesand to stop pulp infections. This means that pain reactions areeliminated and pulp infections are to a certain extent cured. The pulpremains vital.

The topical application of the compounds of formula (I) or formula (II)followed the removal of the carious dentin. The compounds of formula (I)or formula (II) were applied for example in aqueous solution, in a formof gelatinous consistency or on an inert carrier, for example by meansof a cotton wool plug. The overlying cavity was occluded with a cementto seal the margins. The cotton wool plug was left in the cavity forthree to six days. The compounds of formula (I) or formula (II) can beused in concentrations of 0.005 mg/ml to 200 mg/ml. Preferredconcentrations are those ranging from 0.5 mg/ml to 150 mg/ml andparticularly preferred concentrations are those ranging from 10 to 100mg/ml.

Surprisingly, it was observed in a large number of cases that the actionof compounds of formula (I) or formula (II) even resulted in aregeneration of the pulp tissue. This was shown by the fact that, afterextirpation of the infected and inflamed pulp, the nerve needle could beintroduced as far as the foramen physiologicum. About two weeks afterthe topical application of a compound of formula (I) or formula (II), aburgeoning of fresh pulp tissue was observed which was characterized inthat the vertical canal volume was found to have shrunk when inspectedwith instruments, and fresh pulp tissue had grown out again into thecanal in the direction of the crown. This pulp tissue was vital.

Prophylaxis of Dentin Wounds

In the treatment of carious defects or after the preparation of dentinsurfaces to receive e.g. fillings, inlays, onlays, crowns or bridges,dentinal tubules which are directly connected to the pulp, and henceprovide access to the pulp, are cut. Each prepared dentin surface iscovered by an organic layer and preparation residues (smear layer). Ifthe preparatory work is also carried out in dentin modified by caries,said surface normally contains microorganisms. The usual practice is toflush the dentin wound with hydrogen peroxide and then carefully dry itwith the air syringe. Even when the cavity walls are ‘hard to the probe’after removal of the caries and preparation of the cavity, and thecavity has been treated with disinfectants, there is still thepossibility that microbes have already advanced further in the dentinaltubules in the direction of the pulp and are unreachable bydisinfectants. This can cause dentin hypersensitivities and subsequentlysecondary caries.

It has now been found that the prophylactic topical use of the compoundsof formula (I) or formula (II) after every preparation associated withcarious defects in the dentin region can also destroy microbes whichhave advanced well into the dentinal tubules, and that said compoundsthus have an advantageous effect on the tooth-preserving procedures. Forthis reason, after removal of the carious regions, the compounds offormula (I) or formula (II) are applied to the prepared cavities andrubbed in. Said compounds are applied in the form of solutions, gels orsuspensions to form a local depot with an antibiotic action before thereliner is placed on and/or in the fundament of the inlays, onlays,crowns or bridges. This results in the effective destruction of theresidual pathogens not only on the surface of the cavity, but also inthe dentinal tubules. A further advantage is that the tubule structureis not modified or denatured here, as is frequently the case with thecurrent procedures using dentin protecting agents and impregnatingagents. The microbe-free conditions achieved in this way have apermanent beneficial effect on prosthetic procedures since dentinhypersensitivities and subsequently secondary caries are effectivelyavoided.

The application of the compounds of formula (I) or formula (II) caneither replace or complement the disinfecting treatment with hydrogenperoxide. The compounds of formula (I) or formula (II) can be applied indissolved form or as a gel, optionally in the presence of solubilizersto promote a deep penetration of the chemotherapeutic agents into thedentinal tubules. Gels are used in the provisional care of dentin woundsand solutions are preferably used before the definitive fixing of e.g.crowns and bridges. The solutions or gels of the chemotherapeutic agentsused are applied to the prepared dentin surfaces and gently rubbed in.Residues are then removed, for example with a cotton wool swab or airjet. Inlays, onlays, crowns or bridges can then be fixed. The compoundsof formula (I) or formula (II) can be used in concentrations of 0.005mg/ml to 200 mg/ml. Preferred concentrations are those ranging from 0.5mg/ml to 150 mg/ml and particularly preferred concentrations are thoseranging from 10 to 100 mg/ml.

Topical Treatment of the Infected Root Canal and the Periapical Region

In the conventional method normally used nowadays for the topicaltreatment of the infected root canal and the periapical region, failurescan be expected if, after extensive infections of the pulp and hence ofthe root canal, the extremely difficult diagnosis was establishedincorrectly. In these cases pathogenic microbes are present in thelateral branches of the pulp, in the apical delta, in the periapicalregion and in the outer dentin layer of the pulp cavity. It is knownthat infected tissue cannot be completely removed with instruments inmany of these canal regions because of the anatomical conditions. Thediverse branches, for example an apical delta or lateral branches, andthe medullary canals cannot normally be reached and prepared withinstruments. The usual disinfectants are also often unsuccessful. Aparticularly difficult situation arises when the microbes have advancedbeyond the root canal aperture (foramen apicale). This periapical regioncannot be reached with root canal instruments or disinfectants in theform of root canal inserts.

In the conventional treatment, the pulp is removed with a nerve needleand the canal is prepared using root canal cutting instruments. This isto be understood as meaning the widening of the canal lumen and theremoval of the infected canal wall. The mechanical preparation iscombined with the use of chemical agents. The definitive root filling iscarried out after completion of this treatment.

It has now been found, surprisingly, that the compounds of formula (I)or formula (II) can also be used for the topical treatment of theinfected root canal and the periapical region. It was found that thecompounds of formula (I) or formula (II) destroy all the microbesoccurring in the root canal and in the periapical region, includingthose in all the mechanically inaccessible branches of the root canaland beyond the root tip in the periapical region. No bacterialresistances were found when using the compounds of formula (I) orformula (II). This behaviour of the compounds of formula (I) or formula(II) makes it possible to dispense with an extensive preparation in theform practised hitherto.

In the clinical use of the compounds of formula (I) or formula (II), thepulp residues are removed first. The preparation of the canals iscarried out with minimum discomfort for the patient. The canals are thenflushed with hydrogen peroxide. Other methods of disinfection can beomitted. The compounds of formula (I) or formula (II), in a liquid formof administration, are then introduced into the root canal underpressure using a cannula. The compounds of formula (I) or (II) are theninjected in dissolved form or in a gelatinous form of administration.The root canal is subsequently occluded in the crown region, first witha cotton wool plug and then with zinc phosphate cement to seal themargins. If the canals are not gangrenous, the antibiotics remain in thecanals for 3 days. If the canals are gangrenous, it has provedadvantageous to renew the application for a further three days. Thistreatment results in a successful therapy of infected root canals and ofthe apical region. The compounds of formula (I) or formula (II) can beused in concentrations of 0.005 mg/ml to 200 mg/ml. Preferredconcentrations are those ranging from 0.5 mg/ml to 150 mg/ml andparticularly preferred concentrations are those ranging from 10 to 100mg/ml.

Topical application to the root canal can also advantageously becomplemented by the local injection of a solution of the compounds offormula (I) or formula (II) into the periodontal interstice. In thisapplication technique, which is known from intraligamental anaesthesia,the tooth is completely flooded with the antibacterial solution of thecompounds of formula (I) or formula (II) in the entire root region. Thiseffectively destroys the microbes which have invaded the periodontalinterstice and the periapical region. Preferred forms of administrationof the intraligamental injection are solutions of the compounds offormula (I) or formula (II) in concentrations of 0.005 mg/ml to 200mg/ml. Preferred concentrations are those ranging from 0.5 mg/ml to 150mg/ml and particularly preferred concentrations are those ranging from 1to 100 mg/ml.

One particular advantage of using the compounds of formula (I) orformula (II) is that it is possible to preserve teeth which in the pastoften had to be extracted or on which a root tip resection had to beperformed. The consequential costs, e.g. of preparing a dentalprosthesis, can be expected to fall markedly.

Topical Treatment of Periodontal Diseases

Periodontal diseases are often the consequence of poor oral hygiene andin many cases are completely cured by local procedures, e.g. tartarremoval. However, the success depends on the pocket depth and on whetherthe pathogenic microbes can be removed by supragingival scaling. If thistreatment procedure is not successful, combination with the localapplication of antibiotics is recommended. The usual procedure is thelocal application of tetracyclines by means of threads. These are pushedinto the gingival pocket for several days. The advantage of this methodis that an operative intervention can be avoided in many cases.

It has now been found, surprisingly, that the compounds of formula (I)or formula (II) are also suitable for the treatment of periodontaldiseases. To do this, threads or so-called chips impregnated withsolutions or gelatinous preparations of the compounds of formula (I) orformula (II) are inserted in the gingival pocket. A possible alternativeis to use medicament carriers in the form of trays covering the teethand gingiva. Before they are applied, the gelatinous applications of thecompounds of formula (I) or formula (II) are instilled into the gingivalpockets. In addition, the gel containing the compounds of formula (I) orformula (II) can also be placed in the medicament carrier. This use ofmedicament carriers is advantageous because the treatment time can bereduced by the rapid onset of action to about 15 to 30 minutes, so thetreatment can be carried out directly in the surgery. The compounds offormula (I) or formula (II) can be used in concentrations of 0.005 mg/mlto 200 mg/ml. Preferred concentrations are those ranging from 0.5 mg/mlto 200 mg/ml and particularly preferred concentrations are those rangingfrom 10 to 150 mg/ml.

Periodontal diseases can also be treated by administering the compoundsof formula (I) or formula (II) by intraligamental injection, it beingpossible to use concentrations ranging from 0.005 mg/ml to 200 mg/ml,preferably from 0.5 mg/ml to 200 mg/ml. For the antibiotics commonlyused nowadays, such as tetracyclines, an intraligamental injection isnot reasonable since these compounds with a predominantly bacteriostaticaction are quickly washed out due to the rapid fluid exchange in theperiodontal interstice, and cannot develop their action. Tetra-cyclinescan therefore only develop their effects via depot formulations. Bycontrast, the compounds of formula (I) or formula (II) have a very rapidand also bactericidal action, so their residence time in the periodontalinterstice is sufficient to destroy the microbes.

The treatment procedures were characterized by being very effective inthat they covered the entire bacterial spectrum involved in periodontaldiseases. The cure rates were very high. As a rule, the treatmentprocedure was also markedly quicker than those conventionally usedhitherto. Satisfactory clinical results were generally obtained afteronly the third rest period. The prospects of success of this novelmethod of treating periodontal diseases have been substantially improvedby the use of compounds of formula (I) or formula (II). In many casesthis approach can avoid an operative intervention.

It was found, surprisingly, that when the compounds of formulae (I) and(II) were applied to the gingival pocket, the gingival tissueregenerated very rapidly, reached a firm consistency and no longer bled.Accordingly, the topical and/or local application of the compounds offormulae (I) and (II) leads to a rapid regeneration of the periodontaltissues. This in turn leads to a rapid regrowth of the tooth-supportingtissues and a reattachment of the teeth.

Topical Treatment of Osseomucosal Wounds

Bacterial infections of the bone and soft tissues in the mouth and jawregion and in the face often have odontogenous causes. The origin isusually pulp-dead teeth, root residues, odontogenous cysts, dentitiodifficilis and progressive periodontal diseases. Odontogenous abscessesare usually exposed surgically and drained until the cause has beeneliminated. The various infections in the oral region require differenttherapeutic procedures. Thus it is generally possible to dispense with asystemic chemotherapy, for example in the case of infections nearalveolar processes, whereas e.g. the treatment of phlegmons alwaysrequires the systemic administration of antibiotics. As a rule, however,combination with the topical application of antibiotics is advisable.

It has been found that the compounds of formula (I) or formula (II) canalso be used for the topical treatment of osseomucosal wounds, having abeneficial effect on the therapy. Topical use of the compounds offormula (I) or formula (II) normally effects a rapid subsidence of theinflammatory symptoms and an early onset of healing. It has beenobserved that the healing process normally occurs much more rapidly thanin the methods in common use today. The compounds of formula (I) orformula (II) thus have an extremely positive effect, i.e. acceleratingeffect, on the wound healing process.

Application is effected by flushing and/or by means of strip insertsimpregnated with compounds of formula (I) or formula (II). They are tobe used for example for postoperative infections following dentosurgicalinterventions (extractions). For this purpose the gel containing thecompound of formula (I) or formula (II) is syringed directly into theextraction wound or onto a collagen sponge which remains in theextraction wound. The wound is closed for about half an hour by bitingon a tampon. Prophylactic applications have been particularly successfulafter the extraction of teeth with focal infections.

Liquid forms of administration suitable for flushing fistulae are thosecontaining the compounds of formula (I) or formula (II) inconcentrations of 0.005 mg/ml to 250 mg/ml. Preferred concentrations arethose ranging from 0.5 to 100 mg/ml. Forms suitable for coating stripsare gels containing the compounds of formula (I) or formula (II), aswell as aqueous solutions or suspensions. These applications can containthe compounds of formula (I) or formula (II) in concentrations of 0.005mg/ml to 200 mg/ml. Preferred concentrations for solutions are thoseranging from 0.1 to 50 mg/ml. Gelatinous forms of administration inconcentrations of 25-150 mg/ml are preferred in the case of stripinserts.

Wound Care

Postoperative wound infections can generally occur in cases ofinadequate infection prophylaxis following surgical interventions.Posttraumatic wound infections can arise due to cuts, stings, bruises,bites or gunshot wounds. Local perioperative prophylaxis can be carriedout in the case of aseptic operations with a slight risk of infection.It is also possible to use local perioperative prophylaxis in additionto systemic perioperative prophylaxis, for example in the case ofinfections with an increased risk of infection, such as implantations,heart operations, transplantations, neurosurgical operations, operationsin a highly contaminated area such as the oral cavity, oesophagus,rectum or colon, hysterectomy, bile duct operations, operations onpatients with lowered resistance, or amputations. The local treatment offirst, second or third degree burns can be administered prophylacticallyor after infection. Antibacterial local treatment is of great benefitespecially in the case of severe burns. Examples of hand infections arepanaritium cutaneum, panaritium subcutaneum, panaritium ossale,panaritium articulare or tendovaginitis purulenta. In postoperativesepsis the infected wounds can be rendered substantially or completelyfree of microbes by the topical application of antibacterial agents.Gangrenes can be handled by local treatment with antibiotics in additionto therapy with parenteral antibiotics. Examples of acute bacterial skininfections are pyoderma, erysipelas, furuncles, carbuncles, phlegmons,abscesses, ulcus cruris, diabetic foot, infected decubital ulcers, bloodblisters, erysipeloids or erythrasma. Examples of chronic bacterial skininfections are lupus vulgaris, swimming-pool granuloma, Buruli ulcers oractinomycosis. Secondary bacterial infections occur for example in virusinfections such as herpes simplex, herpes zoster or chicken-pox.Secondary bacterial infections of dermatoses occur for example ineczema, the exudation stage of neurodermatitis, vesicular dermatoses orcontact dermatitis.

Milder and moderate forms of acne and rosacea can also be treatedlocally. In all the cases mentioned, local application of the compoundsof formula (I) or formula (II) can be used either on its own or inaddition to systemic application.

Local application of the compounds of formula (I) or formula (II) hasproved advantageous because the broad efficacy of these compounds alsomakes it possible to treat mixed infections. Previous topicalantibiotics have only a restricted spectrum of action and hence are lesseffective. Another advantage of the compounds of formula (I) or formula(II) is the very rapid onset of the antibacterial action. This allows atherapeutic response while the patient is still in the surgery. Thesecompounds of formula (I) or formula (II) have an excellent bactericidalaction and hence are superior to the current topical antibiotics, whichoften have only a bacteriostatic action and accordingly have to be usedmuch more frequently and for much longer periods. Another advantage ofthe compounds of formula (I) or formula (II) compared with current localantibiotics is their good tissue penetration. Their penetration throughthe intact skin also allows the successful local treatment of deeperskin infections. The fact that the compounds of formula (I) or formula(II) have a considerably lower potential than conventional localantibiotics for the generation of bacterial resistance is to be regardedas a further advantage. This enables them to be used much more safely.Another advantage of the compounds of formula (I) or formula (II) is agenerally observable accelerating effect on wound healing. An additionaladvantage of the local use of compounds of formula (I) or formula (II)is the prevention of complications such as lymphangitis, sepsis orchronic local infections.

Surprisingly, topical application of the compounds of formula (I) orformula (II) has also proved particularly effective in the therapy ofdiabetic foot syndrome. According to current medical practice, anylesion found to have local inflammation, with or without signs ofsystemic infection, demands immediate treatment with a broad-spectrumantibiotic. It has to be taken into account here that the inflammatoryprocess normally involves a mixed infection with Gram-positive andGram-negative microbes and with anaerobes and aerobes. Initially, thesystemic administration of amoxicillin, clavulanic acid or clindamycin,each in combination with a gyrase inhibitor, proved effective. Accordingto the result of the wound smear taken prior to the administration ofantibiotics, the antibiosis can then be targeted. However, the timerequired for antibiotic therapy, especially in the case of osteomyeliticdefects, is the subject of controversial discussion. The systemicadministration of high doses of antibiotics for a period of months seemspointless if the X-ray examination shows no detectable tendency of theosteolysis to heal; a surgical intervention will become unavoidable insuch a case.

In the therapy currently used for diabetic foot, an essentialprerequisite for a cure without complications is a wound free ofinfection. Therefore, if the wound is infected, rapid and reliabletreatment of the infection is of the highest priority. A local orsystemic antibiotic therapy involves the risk of allergy and thedevelopment of resistance. Dressings consisting of active charcoal andelemental silver have proved particularly satisfactory. Non-toxicelemental silver controls local infection very effectively. Activecharcoal binds microorganisms and cell detritus and makes it possible toremove the unwanted particles when the dressing is changed. Localirritations or allergies and the development of resistance are excludedand the necessary moist environment is assured at the same time. Inmodern wound treatment, dyes, with the exception of PVP/iodinecomplexes, are no longer important as disinfectants. Potassiumpermanganate has dosage problems and can cause severe skin burns.Ethacridine lactate has a high allergy rate and only a limitedantimicrobial efficacy. Merbromin, which contains mercury, is highlytoxic, impairs granulation and has disposal problems. Other dyes, e.g.brilliant green, methyl violet and fuchsin, are obsolete because oftheir low efficacy and especially because of their damaging effect onthe epithelium.

Accordingly, in the current state of the art, the treatment of diabeticfoot is also in need of topical and/or local antibiotics which have ahigh activity against the microbes occurring in wounds, have a rapidaction, have a good local tolerability, elicit a low tendency togenerate antibiotic resistance, are easy to administer topically and/orlocally, place a minimum system burden on the organism when appliedtopically/locally, have a good tissue penetration, are also suitable forthe treatment of deep infections and furthermore accelerate the woundhealing process.

It has now been found that topical application of the compounds offormula (I) or formula (II) can also achieve a satisfactory outcome inthe therapy of diabetic foot syndrome. This was demonstratedparticularly by the fact that, in patients with severe microangiopathiesof the feet accompanying diabetic foot syndromes, attempted systemictreatments with Avalox 400 (moxifloxacin) and/or Clont 400(2-methyl-5-nitro-1H-imidazol-1-ethanol) brought no significant changesin findings since these active ingredients were only able to achievevery low tissue concentrations after systemic administration because ofpronounced micro-angiopathies. Surprisingly, however, topicalapplication of the compounds of formula (I) or formula (II) led tosignificant improvements in the pathological process. Ulcers ofdifferent degrees of severity (D I to D V ulcers) could be treated.Greasy ulcers became clean, encrusted and smaller in size and evenhealed completely. This treatment was successful after several topicalapplications of the compounds of formula (I) or formula (II) at weeklyintervals, said compounds being applied to the wound directly indissolved form or, for example, as a gel or by means of impregnatedcompresses or dressings. These compounds of formula (I) or formula (II)can be applied to the wound in concentrations of 0.005 mg/ml to 200mg/ml, preferred concentrations for solutions or gels being thoseranging from 0.1 to 150 mg/ml. In the case of impregnated compresses ordressings, gelatinous forms of administration can be used inconcentrations of 25-150 mg/ml.

It has further been found that local and/or topical application of thecompounds of formula (I) or formula (II) is also beneficial inveterinary medicine. Recent studies have shown that, in many countries,two-thirds of dogs and more than 80% of cats over four years of agerequire dental treatment. Moreover, more than 10% of cats and 7.5% ofdogs over 4 years of age suffer from severe periodontitis, which canlead to renal, hepatic and cardiac infections. It has now been found,surprisingly, that the compounds of formula (I) or formula (II) are alsosuitable for the treatment of dental diseases in animals. Endodontaltreatments can be carried out using the same methods and the same activeingredient concentrations of the compounds of formula (I) or formula(II) as those explained above for treatments in human dental medicine.For the treatment of periodontal diseases, threads impregnated withsolutions or gelatinous preparations of the compounds of formula (I) orformula (II) are inserted in the animal's gingival pocket. Analternative possibility is to use silicone trays. The compounds offormula (I) or formula (II) can be used in concentrations of 0.005 mg/mlto 200 mg/ml. Preferred concentrations are those ranging from 0.5 mg/mlto 200 mg/ml and particularly preferred concentrations are those rangingfrom 10 to 150 mg/ml.

When foreign bodies are introduced into the oral region of an animal fora prolonged period of time, reaction episodes can ensue, so it is oftenadvantageous to treat periodontal diseases with compounds of formula (I)or formula (II) by direct instillation into the gingival pocket, byintraligamental injection or by means of a medicament carrier, forexample a silicone tray. In the last case the animal to be treated isanaesthetized and a lump of workable silicone impression material, asconventionally used in human dental medicine, is pressed against theupper jaw. After the mouth has been closed, an impression of the lowerteeth is made and, by pressing the still plastic material, the entiremarginal regions of the gingiva are covered so as to overlap in thebuccal cavity. After curing, the total impression of the upper and lowerteeth and the gingival areas is removed and a compound of formula (I) orformula (II) is instilled into the gingival pockets and optionallyplaced in the cavities of the impression. The mould is placed on theanimal's jaws again. The mouth is kept closed for a further 15 to 30minutes, allowing the compounds of formula (I) or formula (II) to maketopical contact with the tissue.

Topical and/or local application of the compounds of formulae (I) and(II) effects a rapid destruction of the bacteria and a rapidregeneration of the periodontal tissues. This leads to a rapid regrowthof the tooth-supporting tissues and a reattachment of the teeth. Afurther advantage of this method of treatment is that the animal'sstrong mouth odour is effectively and causally controlled. The compoundsof formula (I) or formula (II) can be used as solutions or gels inconcentrations ranging from 0.005 mg/ml to 200 mg/ml, preferably from0.5 mg/ml to 200 mg/ml.

The compounds of formula (I) or formula (II) can also be used incombination with other anti-infective agents such as antibacterial,antifungal or antiviral substances.

The compounds of formula (I) or formula (II) can be used inconcentrations of 0.005 mg/ml to 200 mg/ml. Preferred concentrations arethose ranging from 0.5 mg/ml to 200 mg/ml and particularly preferredconcentrations are those ranging from 10 to 150 mg/ml.

The compounds of formula (I) or formula (II) can be used as solutions,gels, suspensions, emulsions or liposomes or in micelles. Examples ofsolutions are aqueous solutions in the presence of solubilizers.Examples of solubilizers are salts, polyols, sugar alcohols, polyglycolsor co-solvents such as glycerol, ethylene glycol, propylene glycol,furfural, N,N-dimethylformamide, methanol, ethanol, i-propanol,n-propanol or acetone. Aqueous gels are prepared by the addition ofgelling agents such as pectins, ethylene glycol monomethacrylate gel,alginates, hydroxyethyl cellulose, carboxymethyl hydroxyethyl cellulose,polyglyceryl methacrylates or polysaccharides. Other suitable additivesare thickeners such as cellulose, alkyl cellulose, hydroxyethylcellulose, agar-agar, carboxymethyl guar and cellulose ethers, orhydrotropic solubilizers such as ethylenediamine, urea or cyclodextrins.The galenical forms can also contain solubilizers such as surfactants,or preservatives. Examples of possible suspension constituents aretragacanth, cellulose, wetting agents, glycols, polyols, mucins orcellulose ethers. Possible emulsion constituents are emulsifiers such aspolysorbates, surfactants, lecithins, mucins, gelatin or carboxymethylcellulose. Other suitable forms of administration are dental pocketinserts consisting of an inert carrier material, which are impregnatedwith the active ingredient and optionally other auxiliary substances andgradually release the active ingredient by dissolution. Examples ofpossible forms of administration for root fillings are tampons, cottonwool plugs or foam pellets. Application in the case of soft tissueinfections can be effected with strips or thread inserts. It is alsopossible to use pharmaceutical substances or auxiliary substances forosmotic adjustment. Other possible auxiliary substances for formulatingthe compounds of formula (I) or formula (II) are antioxidants, chelatingagents, disinfectants, dispersants, emulsion stabilizers, hydrocolloids,preservatives, solubilizers, wetting agents, quaternary ammoniumcompounds, stabilizers, suspending agents or thickeners. Theabove-mentioned constituents can also be used in combination with oneanother.

Suitable stable gelatinous formulations are those which, apart from thecompounds of formula (I) or formula (II), are composed of polyethers,modified celluloses and water. Preferred gel formulations are thosecontaining the compounds of formula (I) or formula (II) in mixtures ofpropylene glycol, Tween 20 solution and muc. hydroxyethyl cellulose.Preferred compositions consist of compounds of formula (I) or formula(II) in amounts of 0.001 to 100 mg/ml, polypropylene glycol in amountsof 5 to 250 mg/ml, 1% Tween 20 solution in amounts of 5 to 200 mg/ml andmuc. hydroxyethyl cellulose ad 1 g/ml. Particularly preferred gelatinousformulations consist of the compounds of formula (I) or formula (II) inamounts of 1 to 100 mg/ml, propylene glycol in amounts of 50 to 200mg/ml, 1% Tween 20 solution in amounts of 3 to 150 mg/ml and muc.hydroxy cellulose ad 1 g/ml.

The Examples which follow serve to illustrate the present inventionwithout however limiting the general spirit of the invention.

EXAMPLES Examples of Different Formulations Example 1

Moxifloxacin•HCl solution moxifloxacin hydrochloride 500 mg aqua proinjectione ad 100 ml

Example 2

High-viscosity formulation: moxifloxacin•HCl gel moxifloxacinhydrochloride 1.0 g hydroxyethyl cellulose 0.5 g propylene glycol 1.5 gdistilled water ad 10.0 g

Example 3

Low-viscosity formulation with stabilizer: moxifloxacin•HCl gelmoxifloxacin hydrochloride 1.0 g hydroxyethyl cellulose 0.25 g propyleneglycol 1.5 g 1% Tween 20 solution 1.0 g distilled water ad 10.0 g

Example 4

Moxifloxacin•HCl gel moxifloxacin hydrochloride 0.1 g hydroxyethylcellulose 0.25 g propylene glycol 1.5 g 1% Tween 20 solution 1.0 gdistilled water ad 10.0 gA. Endodontal DiseasesA. 1. Topical Treatment of Pulpitis Due to Carious Diseases

Patient A 1.1 (Male, 43 Years).

Clinical diagnosis: tooth 24, mesial carious defect (enamel/dentin),tooth vital, increased sensitivity to cold. Course of treatment: removalof caries. Residual dentin covering very slightly softened. Pelletinsert impregnated with moxifloxacin hydrochloride gel (25 mg/ml),provisional cavity occlusion. Check-up after 4 days: patient wassymptom-free. Relining with dropsin, final filling with composite.Check-up after 3 weeks: tooth vital, patient symptom-free.

Patient A 1.2 (Male, 33 Years).

Clinical diagnosis: teeth 11, 13, major distal and mesial cariousdefects (enamel/dentin), all teeth vital, tooth 11 sensitive to cold,tooth 13 slightly sensitive to heat. Course of treatment: removal ofcaries. Residual dentin covering hard. Pellet inserts with moxifloxacinhydrochloride gel (50 mg/ml), provisional cavity occlusion. Check-upafter 1 week: teeth 11 and 13 symptom-free. Relining with dropsin, finalfilling with composite. Check-up after 14 days: teeth vital, patientsymptom-free.

Patient A 1.3 (Female, 18 Years).

Clinical diagnosis: tooth 24, major distal carious defect(enamel/dentin), tooth vital, sensitive to cold, sweet and sour. Courseof treatment: removal of caries. Residual dentin covering hard. Pelletinsert with moxifloxacin hydrochloride gel (25 mg/ml), provisionalcavity occlusion. Check-up after one week: still slight discomfort ofunknown origin, repetition of insert. Check-up after 3 days: toothvital, patient symptom-free. Relining with dropsin, final filling withglass ionomer.

Patient A 1.4 (Male, 23 Years).

Clinical diagnosis: tooth 11, major mesial carious defect, tooth vital,sensitivity to heat and cold, night pain. Course of treatment: removalof caries. Residual dentin covering slightly softened. Pellet insertswith moxifloxacin hydrochloride gel (50 mg/ml), provisional cavityocclusion. Check-up after 7 days: patient symptom-free, tooth vital.Relining with zinc phosphate cement, final filling with glass ionomer.

Patient A 1.5 (Male, 43 Years).

Clinical diagnosis: tooth 13, major distal carious defect, tooth weaklyvital, sensitivity to cold, night pain. Course of treatment: removal ofcaries. Residual dentin covering hard. Pellet insert with moxifloxacinhydrochloride gel (50 mg/ml), provisional cavity occlusion. Check-upafter 4 days: patient symptom-free, tooth vital. Relining with dropsin,final filling with composite.

Patient A 1.6 (Female, 42 Years).

Clinical diagnosis: tooth 36, major mesial carious defect, tooth withreduced vitality, sensitivity to cold and heat, night pain. Course oftreatment: removal of caries, pellet insert with moxifloxacinhydrochloride gel (50 mg/ml), provisional cavity occlusion. Check-upafter 6 days: still slight sensitivity to heat and cold. Repetition ofinsert. Check-up after 7 days: patient symptom-free, tooth vital.Relining with zinc phosphate cement, final filling with composite.

Patient A 1.7 (Female, 18 Years).

Clinical diagnosis: tooth 44, major mesial carious defect, tooth withreduced vitality, sensitivity to cold, night pain. Course of treatment:removal of caries. Residual dentin covering slightly softened. Pelletinserts with moxifloxacin hydrochloride gel (50 mg/ml), provisionalcavity occlusion. Check-up after 4 days: patient symptom-free, reliningwith zinc phosphate cement, final filling with composite.

Patient A 1.8 (Male, 38 Years).

Clinical diagnosis: tooth 36, major distal carious defect, tooth withreduced vitality, sensitivity to cold, heat, sweet and sour, slightlysensitive to percussion, night pain. Course of treatment: removal ofcaries. Residual dentin covering slightly softened. Pellet insert withmoxifloxacin hydrochloride gel (50 mg/ml), provisional cavity occlusion.Check-up after 3 weeks: patient symptom-free, tooth vital, relining withzinc phosphate, final filling with composite.

Patient A 1.9 (Female, 50 Years).

Clinical diagnosis: tooth 27, major distal carious defect, tooth vital,sensitivity to cold, slight sensitivity to heat, slight night pain.Course of treatment: removal of caries. Residual dentin coveringsoftened. Pellet insert with moxifloxacin hydrochloride gel (25 mg/ml),provisional occlusion. Check-up after 7 days: patient symptom-free,tooth vital.

Patient A 1.10 (Male, 17 Years).

Clinical diagnosis: teeth 16, 17, 27, 36, 37, 46 with occlusal caries,teeth vital, sensitivity to cold, sweet and sour, sometimes to heat, notlocalizable. Course of treatment: removal of caries. Residual dentincoverings hard. Pellet inserts with moxifloxacin hydrochloride gel (50mg/ml), provisional cavity occlusion. Check-up after 14 days: patientsymptom-free, teeth vital. Relining with dropsin, final filling withcomposite.

Patient A 1.11 (Male, 33 Years).

Clinical diagnosis: tooth 22, distal carious defect (enamel/dentin),tooth vital, slight sensitivity to heat. Course of treatment: removal ofcaries, residual dentin covering very slightly softened. Pellet insertimpregnated with grepafloxacin gel (25 mg/ml), provisional cavityocclusion. Check-up after 5 days: patient was symptom-free. Reliningwith zinc phosphate cement, final filling with composite. Check-up after4 weeks: tooth vital, patient symptom-free.

Patient A 1.12 (Male, 38 Years).

Clinical diagnosis: teeth 22, 23 with major distal carious defects(enamel/dentin), teeth vital, sensitivity to cold. Course of treatment:removal of caries, residual dentin covering hard. Pellet inserts withgrepafloxacin gel (50 mg/ml), provisional cavity occlusion. Check-upafter 1 week: teeth symptom-free. Relining with dropsin, final fillingwith composite. Check-up after 14 days: teeth vital, patientsymptom-free.

Patient A 1.13 (Female, 48 Years).

Clinical diagnosis: tooth 14, major mesial carious defect(enamel/dentin), tooth vital, sensitivity to cold and sour. Course oftreatment: removal of caries, residual dentin covering hard. Pelletinsert with gemifloxacin mesylate gel (25 mg/ml), provisional cavityocclusion. Check-up after 3 weeks: still slight discomfort. Repetitionof insert. Check-up after 4 days: tooth vital, patient symptom-free.Relining with dropsin, final filling with glass ionomer.

Patient A 1.14 (Male, 53 Years).

Clinical diagnosis: tooth 13, major mesial carious defect, tooth vital,sensitivity to heat, night pain. Course of treatment: removal of caries,residual dentin covering slightly softened. Pellet inserts withlevofloxacin gel (50 mg/ml), provisional cavity occlusion. Check-upafter 14 days: patient symptom-free, tooth vital. Relining with dropsin,final filling with composite.

Patient A 1.15 (Male, 22 Years).

Clinical diagnosis: tooth 44, major mesial carious defect, tooth vital,sensitivity to cold, night pain. Course of treatment: removal of caries,residual dentin covering leathery. Pellet insert with trovafloxacinmesylate gel (50 mg/ml), provisional cavity occlusion. Check-up after 9days: patient symptom-free, tooth vital. Relining with dropsin, finalfilling with composite.

Patient A 1.16 (Female, 15 Years).

Clinical diagnosis: tooth 46, major distal carious defect, tooth withreduced vitality, sensitivity to cold and heat. Course of treatment:removal of caries, pellet insert with sparfloxacin gel (25 mg/ml),provisional cavity occlusion. Check-up after 4 days: still slightsensitivity to heat. Repetition of insert. Check-up after 14 days:patient symptom-free, tooth vital. Relining with dropsin, final fillingwith composite.

A.2. Prophylaxis of Dentin Wounds

Patient A 2.1 (Male, 30 Years).

Clinical diagnosis: teeth 33 and 36, carious defects on both teeth.Teeth vital. Course of treatment: preparation of teeth 33 and 36.Making-up of provisional bridge. Application of moxifloxacinhydrochloride solution (25 mg/ml) to cavity, drying in gentle air jet.Fixing of bridge with provisional cement. After 8 days, definitiveinsertion of bridge with zinc phosphate cement. Check-up after 3 weeks:patient symptom-free.

Patient A 2.2 (Male, 48 Years).

Clinical diagnosis: teeth 22, 23, 24 with small distal carious defects(enamel/dentin), all teeth vital, sensitivity to cold. Course oftreatment: removal of caries, smear with moxifloxacin hydrochloridesolution (50 mg/ml), provisional cavity occlusion. Check-up after 2weeks: teeth symptom-free. Relining with dropsin, final filling withcomposite. Check-up after 4 weeks: teeth vital, patient symptom-free.

Patient A 2.3 (Female, 28 Years).

Clinical diagnosis: teeth 14, 15, 16, 17 with cervical erosions(enamel/dentin), sensitivity to cold and sweet. Course of treatment:preparation, smear with moxifloxacin hydrochloride solution (50 mg/ml),gentle drying in air jet. Adhesive restoration with composite. Check-upafter 3 weeks: patient symptom-free.

Patient A 2.4 (Male, 33 Years).

Clinical diagnosis: teeth 11, 12, 21, 22 with carious defects in firstthird of dentin, teeth vital. Course of treatment: preparation forceramic crowns. Smear with moxifloxacin hydrochloride solution (25mg/ml), drying in gentle air jet, insertion of provisional crowns. After14 days, insertion of definitive crowns with zinc phosphate cement.Check-up after 3 weeks: patient symptom-free.

Patient A 2.5 (Male, 62 Years).

Clinical diagnosis: tooth 44, mesial carious defect in first third ofdentin, sensitivity to cold. Course of treatment: removal of caries,smear with moxifloxacin hydrochloride solution (25 mg/ml), provisionalcavity occlusion. Check-up after 9 days: patient symptom-free. Reliningwith dropsin, final filling with composite.

Patient A 2.6 (Female, 18 Years).

Clinical diagnosis: tooth 43, distal carious defect in first third ofdentin. Course of treatment: removal of caries, smear with moxifloxacinhydrochloride solution (25 mg/ml), relining with dropsin, final fillingwith composite. Patient failed to attend check-up.

Patient A 2.7 (Female, 28 Years).

Clinical diagnosis: teeth 15, 14, 13, 12, 11, 21, 22, 23, 24, 25 withcervical erosions, severe hypersensitivity. Course of treatment:cleaning of eroded regions, smear with sparfloxacin solution (50 mg/ml),gentle drying in air jet. Adhesive restoration with composite.

Patient A 2.8 (Female, 33 Years).

Clinical diagnosis: teeth 13, 14, 15 with mesial and distal cariousdefects in first third of dentin, sensitivity to cold. Course oftreatment: preparation of cavities, removal of caries, smear withtrovafloxacin mesylate solution (25 mg/ml), drying in gentle air jet.Adhesive restoration with glass ionomer cement.

A.3. Topical Treatment of the Infected Root Canal and the PeriapicalRegion

Patient A 3.1 (Female, 40 Years).

Clinical diagnosis: tooth 45, apical periodontitis due to pulpitispurulenta, slight bite discomfort. Slightly widened periodontalinterstice in X-ray, not gangrenous. Course of treatment: canalpreparation down to apex. Canal insert with moxifloxacin hydrochloridesolution (100 mg/ml) by syringe, then topping-up with moxifloxacinhydrochloride gel (100 mg/ml), provisional occlusion. Check-up after 3days: patient symptom-free, root filling with endomethasone. Check-upafter 14 days: patient still symptom-free, final filling with composite.

Patient A 3.2 (Male, 70 Years).

Clinical diagnosis: tooth 23, gangrenous, bite discomfort. X-ray normal.Course of treatment: canal preparation down to apex, canal insert withmoxifloxacin hydrochloride solution (100 mg/ml) by syringe, thentopping-up with moxifloxacin hydrochloride gel (100 mg/ml), provisionalocclusion. Check-up after 14 days: patient symptom-free, canalodourless. Root filling with endomethasone.

Patient A 3.3 (Female, 22 Years).

Clinical diagnosis: tooth 11, apical periodontitis due to gangrene, bitediscomfort. Widened periodontal interstice in X-ray. Course oftreatment: canal preparation down to apex, canal insert withmoxifloxacin hydrochloride solution (50 mg/ml) by syringe, thentopping-up with moxifloxacin hydrochloride gel (50 mg/ml) andintraligamental injection of moxifloxacin hydrochloride solution (50mg/ml). Provisional occlusion. Check-up after 3 days: patientsymptom-free, canal odourless.

Patient A 3.4 (Male, 40 Years).

Clinical diagnosis: tooth 11, apical periodontitis due to pulpitispurulenta, not gangrenous, bite discomfort. Widened periodontalinterstice in X-ray. Course of treatment: canal preparation down toapex, root canal insert with moxifloxacin hydrochloride gel (50 mg/ml),provisional occlusion. Check-up after 3 days: patient symptom-free. Rootfilling with endomethasone, provisional occlusion. Check-up after 3weeks: patient still symptom-free. Final filling with composite.

Patient A 3.5 (Female, 43 Years).

Clinical diagnosis: tooth 35, apical periodontitis due to gangrene,slight bite discomfort. Weak translucence visible in X-ray. Course oftreatment: canal preparation down to apex not possible. Root canalinsert with moxifloxacin hydrochloride solution (50 mg/ml) by syringe,then topping-up with moxifloxacin hydrochloride gel (50 mg/ml) andintraligamental injection of moxifloxacin hydrochloride solution (50mg/ml). Check-up after 7 days: no gangrenous odour, no bite discomfort.Root filling with N2 medical. Check-up after 7 days: patientsymptom-free. Final filling with composite.

Patient A 3.6 (Male, 29 Years).

Clinical diagnosis: tooth 36, apical periodontitis due to gangrene, bitediscomfort. X-ray normal. Course of treatment: canal preparation down toapex, root canal insert with moxifloxacin hydrochloride gel (50 mg/ml)and intraligamental injection of moxifloxacin hydrochloride solution (50mg/ml). Check-up after 8 days: no gangrenous odour, patientsymptom-free. Root filling with N2 medical. Check-up after 3 weeks:patient symptom-free. Final filling with composite.

Patient A 3.7 (Female, 50 Years).

Clinical diagnosis: tooth 14, apical periodontitis due to gangrene.Slight bite discomfort. Weak translucence in X-ray. Course of treatment:canal preparation down to apex, root canal insert with moxifloxacinhydrochloride gel (100 mg/ml) and intraligamental injection ofmoxifloxacin hydrochloride solution (50 mg/ml), provisional occlusion.Check-up after 7 days: patient symptom-free. Root filling withendomethasone. Check-up after 3 weeks: patient still symptom-free. Finalfilling with composite.

Patient A 3.8 (Female, 42 Years).

Clinical diagnosis: tooth 34, apical periodontitis due to gangrene, bitediscomfort. Weak translucence visible in X-ray. Course of treatment:canal preparation down to apex not possible. Root canal insert withmoxifloxacin hydrochloride gel (50 mg/ml) and intraligamental injectionof moxifloxacin hydrochloride solution (50 mg/ml), provisionalocclusion. Check-up after 13 weeks: patient symptom-free, canalodour-free. Root filling with endomethasone, final filling with glassionomer.

Patient A 3.9 (Female, 17 Years).

Clinical diagnosis: tooth 46, apical periodontitis due to pulpitispurulenta, slight bite discomfort, tooth not gangrenous. Slightlywidened periodontal interstice at mesial root in X-ray. Course oftreatment: canals prepared down to apex, root canal insert withmoxifloxacin hydrochloride gel (100 mg/ml) and intraligamental injectionof moxifloxacin hydrochloride solution (50 mg/ml). Check-up after 7days: patient symptom-free. Root filling with endomethasone, finalfilling. Patient failed to attend subsequent check-up.

Patient 3.10 (Female, 24 Years).

Clinical diagnosis: tooth 14, fistula in root tip region, toothgangrenous. Slight bite discomfort. Course of treatment: canalpreparation down to apex. Canal and fistula flushed with moxifloxacinhydrochloride solution (50 mg/ml) by syringe, canal insert withmoxifloxacin hydrochloride gel (50 mg/ml) and intraligamental injectionof moxifloxacin hydrochloride solution (50 mg/ml). Canal occluded onlywith cotton wool plug. Check-up after 3 days: patient still notcompletely symptom-free. Canal still had very slight gangrenous odour.Repetition of flushing with moxifloxacin hydrochloride solution (50mg/ml) and canal insert with moxifloxacin hydrochloride gel (50 mg/ml).Check-up after 8 days: patient symptom-free. Root filling withendomethasone. Check-up after 3 weeks: patient symptom-free. Finalfilling with composite.

Patient A 3.11 (Male, 51 Years).

Clinical diagnosis: tooth 34, apical periodontitis due to pulpitispurulenta, not gangrenous, no bite discomfort. Fistula in root tipregion. Weak translucence in X-ray. Course of treatment: canalpreparation down to apex not possible at palatinal root. Root canalinsert with moxifloxacin hydrochloride gel (100 mg/ml), provisionalocclusion. Check-up after 10 days: patient symptom-free. Root fillingwith endomethasone. Patient failed to attend check-up.

Patient A 3.12 (Female, 34 Years).

Clinical diagnosis: tooth 44, fistulation, bite difficulties,gangrenous. Course of treatment: canal preparation down to apex. Rootcanal insert with moxifloxacin hydrochloride solution (50 mg/ml) usingpaper point and intraligamental injection of moxifloxacin hydrochloridesolution (50 mg/ml), provisional occlusion. Check-up after 8 days:patient symptom-free. Root filling with endomethasone, final fillingwith composite.

Patient A 3.13 (Female, 78 Years).

Clinical diagnosis: tooth 15, apical periodontitis due to pulpitispurulenta, slight bite discomfort, not gangrenous. Course of treatment:canal preparation down to apex, canal insert with moxifloxacinhydrochloride solution (50 mg/ml) by syringe and then topping-up withmoxifloxacin hydrochloride gel (50 mg/ml) and intraligamental injectionof moxifloxacin hydrochloride solution (50 mg/ml), provisionalocclusion. Check-up after 9 days: patient symptom-free, root fillingwith endomethasone. Check-up after 10 days: patient still symptom-free,final filling with composite.

Patient A 3.14 (Male, 30 Years).

Clinical diagnosis: tooth 13, gangrenous, bite discomfort, X-ray normal.Course of treatment: canal preparation down to apex, canal insert withmoxifloxacin hydrochloride solution (50 mg/ml) by syringe and thentopping-up with moxifloxacin hydrochloride gel (50 mg/ml) andintraligamental injection of moxifloxacin hydrochloride solution (50mg/ml), provisional occlusion. Check-up after 10 days: patientsymptom-free, canal odourless, root filling with endomethasone.

Patient A 3.15 (Female, 32 Years).

Clinical diagnosis: tooth 31, apical periodontitis due to gangrene, bitediscomfort, widened periodontal interstice in X-ray. Course oftreatment: canal preparation down to apex, canal insert withmoxifloxacin hydrochloride solution (50 mg/ml) by syringe, thentopping-up with moxifloxacin hydrochloride gel (50 mg/ml) andintraligamental injection of moxifloxacin hydrochloride solution (50mg/ml), provisional occlusion. Check-up after 9 days: patientsymptom-free, canal odourless.

Patient A 3.16 (Male, 40 Years).

Clinical diagnosis: tooth 46, apical periodontitis due to pulpitispurulenta, not gangrenous, widened periodontal interstice visible inX-ray. Course of treatment: canal preparation down to apex, root canalinsert with grepafloxacin gel (50 mg/ml), provisional occlusion.Check-up after 3 weeks: patient symptom-free. Root filling withendomethasone, provisional occlusion. Check-up after 1 week: patientstill symptom-free, final filling with composite.

Patient A 3.17 (Female, 33 Years).

Clinical diagnosis: tooth 32, apical periodontitis due to gangrene,slight bite discomfort, weak translucence visible in X-ray. Course oftreatment: canal preparation down to apex not possible. Root canalinsert with grepafloxacin solution (20 mg/ml) by syringe, thentopping-up with grepafloxacin gel (20 mg/ml) and intraligamentalinjection of grepafloxacin solution (50 mg/ml). Check-up after 6 days:no gangrenous odour, no bite discomfort. Root filling with N2 medical.Check-up after 4 days: patient symptom-free. Final filling withcomposite.

Patient A 3.18 (Female, 55 Years).

Clinical diagnosis: tooth 34, apical periodontitis due to gangrene,slight bite discomfort, weak translucence visible in X-ray. Course oftreatment: canal preparation down to apex, root canal insert withtrovafloxacin mesylate gel (100 mg/ml) and intraligamental injection oftrovafloxacin mesylate solution (50 mg/ml), provisional occlusion.Check-up after 12 days: patient symptom-free. Root filling withendomethasone. Check-up after 3 weeks: patient still symptom-free. Finalfilling with composite.

Patient A 3.19 (Female, 22 Years).

Clinical diagnosis: tooth 11, apical periodontitis due to gangrenasimplex. Course of treatment: canal preparation down to apex notpossible. Root canal insert with trovafloxacin mesylate solution (50mg/ml), provisional occlusion. Check-up after 3 weeks: patientsymptom-free, canal odour-free. Root filling with endomethasone, finalfilling with glass ionomer.

Patient A 3.20 (Female, 77 Years).

Clinical diagnosis: tooth 47, apical periodontitis due to pulpitispurulenta, tooth not gangrenous, slightly widened periodontal intersticeat mesial root visible in X-ray. Course of treatment: canals prepareddown to apex. Root canal insert with tosufloxacin tosylate gel (100mg/ml). Check-up after 8 days: patient symptom-free. Root filling withendomethasone, final filling. Patient failed to attend subsequentcheck-up.

Patient A 3.21 (Female, 54 Years).

Clinical diagnosis: tooth 22, fistula in root tip region, toothgangrenous, slight bite discomfort. Course of treatment: canalpreparation down to apex, canal and fistula flushed with moxifloxacinhydrochloride solution (50 mg/ml) by syringe, canal insert withmoxifloxacin hydrochloride gel (50 mg/ml) and intraligamental injectionof moxifloxacin hydrochloride solution (50 mg/ml). Canal occluded onlywith cotton wool plug. Check-up after 8 days: patient still not fullysymptom-free, canal still had very slight odour. Repetition of flushingand insert. Check-up after 10 days: patient symptom-free. Root fillingwith endomethasone. Check-up after 1 week: patient symptom-free. Finalfilling with composite.

Patient A 3.22 (Male, 50 Years).

Clinical diagnosis: tooth 35, apical periodontitis due to pulpitispurulenta, not gangrenous, no bite discomfort. Course of treatment:canal preparation down to apex, root canal insert with tosufloxacintosylate gel (50 mg/ml), provisional occlusion. Check-up after 10 days:patient symptom-free. Root filling with endomethasone. Patient failed toattend check-up.

Patient A 3.23 (Female, 64 Years).

Clinical diagnosis: tooth 34, fistulation, bite difficulties,gangrenous. Course of treatment: canal preparation down to apex, rootcanal insert with grepafloxacin solution (50 mg/ml) using paper point,intra-ligamental injection of grepafloxacin solution (50 mg/ml),provisional occlusion. Check-up after 10 days: patient symptom-free.Root filling with endomethasone, final filling with composite.

B. Topical Treatment of Periodontal Diseases

Patient B 1 (Female, 33 Years).

Clinical diagnosis: teeth 26 and 27, marginal periodontitis with exposedroot cement, pocket depths of 4 to 5 mm, strong foetor ex ore. Course oftreatment: removal of concrement by ultrasound and manually, threadinsert with moxifloxacin hydrochloride gel (50 mg/ml). Covering withGingipac gingival dressing. Check-up after 3 days: patient symptom-free,gingival regions and pockets inflammation-free.

Patient B 2 (Female, 60 Years).

Clinical diagnosis: teeth 14 to 18, severe marginal periodontitis withexposed root cement, pocket depths of 5 to 6 mm. Course of treatment:removal of concrement by ultrasound, thread insert with moxifloxacinhydrochloride gel (50 mg/ml), covering with Gingipac gingival dressing.Check-up after 4 days: patient symptom-free, gingival regions andpockets inflammation-free.

Patient B 3 (Male, 49 Years).

Clinical diagnosis: teeth 24 to 28, marginal periodontitis with exposedroot cement, pocket depths of 4 to 6 mm. Course of treatment: removal ofconcrement by ultrasound and manually, thread insert with moxifloxacinhydrochloride (50 mg/ml), covering with Gingipac gingival dressing.Check-up after 5 days: patient symptom-free, gingival regions andpockets inflammation-free.

Patient B 4 (Female, 20 Years).

Clinical diagnosis: marginal periodontitis in entire upper and lower jawregion, strong foetor ex ore, pocket depths of 4 to 5 mm. Course oftreatment: removal of concrement by ultrasound, medicinal splint withmoxifloxacin hydrochloride gel (0.25 mg/ml) worn for 10 minutes/day for4 days. Check-up after 3 days: patient symptom-free, no moreinflammatory phenomena present.

Patient B 5 (Female, 53 Years).

Clinical diagnosis: tooth 37, marginal periodontitis with exposed rootcement, pocket depths of 5 mm, strong foetor ex ore. Course oftreatment: removal of concrement by ultrasound and manually, threadinsert with moxifloxacin hydrochloride gel (50 mg/ml), covering withGingipac gingival dressing. Check-up after 8 days: patient symptom-free,gingival regions and pockets inflammation-free.

Patient B 6 (Female, 30 Years).

Clinical diagnosis: teeth 25-28, severe marginal periodontitis withexposed root cement, pocket depths of 4 mm. Course of treatment: removalof concrement by ultrasound, thread insert with moxifloxacinhydrochloride gel (50 mg/ml), intraligamental injection of moxifloxacinhydrochloride solution (50 mg/ml), covering with Gingipac gingivaldressing. Check-up after 10 days: patient symptom-free, gingival regionsand pockets inflammation-free.

Patient B 7 (Male, 35 Years).

Clinical diagnosis: teeth 14-17, marginal periodontitis with exposedroot cement, pocket depths of 4 mm. Course of treatment: removal ofconcrement by ultrasound and manually, thread insert with grepafloxacingel (50 mg/ml), intraligamental injection of grepafloxacin solution (50mg/ml), covering with Gingipac gingival dressing. Check-up after 9 days:patient symptom-free, gingival regions and pockets inflammation-free.

Patient B 8 (Female, 33 Years).

Clinical diagnosis: marginal periodontitis in entire upper and lower jawregion, strong foetor ex ore, pocket depths of 3-5 mm. Course oftreatment: removal of concrement by ultrasound, medicinal splint withtrovafloxacin mesylate gel (0.25 mg/ml) worn for 10 minutes/day for 6days. Check-up after 6 days: patient symptom-free, inflammationphenomena no longer present.

C. Topical Treatment of Osseomucosal Wounds

Patient C 1 (Male, 14 Years).

Clinical diagnosis: teeth 011 and 012, wound care after extraction,reimplanted teeth. Course of treatment: resorption, ankylosis andsequestrum in X-ray. Excochleation after wound care. Application ofdepot of moxifloxacin hydrochloride gel (50 mg/ml) by gauze strip.Check-up after 3 days: patient symptom-free, good wound marginadaptation.

Patient C 2 (Male, 16 Years).

Clinical diagnosis: regio 36, wound care after major surgicalinterventions, slight submucosal swelling, fistulation on tooth 36following pulpitis purulenta. Course of treatment: incision, flushingwith moxifloxacin hydrochloride solution (50 mg/ml), strip insert withmoxifloxacin hydrochloride gel (50 mg/ml). Check-up after 3 days:patient symptom-free, good rapid healing process.

Patient C 3 (Female, 34 Years).

Clinical diagnosis: teeth 26 and 46 with apical granulomas, severe bitediscomfort. Course of treatment: extraction at inflammatory stage(osteotomy), no suture. Wound care with gauze impregnated withmoxifloxacin hydrochloride gel (50 mg/ml). Check-up after 2 days:patient symptom-free.

Patient C 4 (Female, 34 Years).

Clinical diagnosis: tooth 48, impacted and displaced. Course oftreatment: wound care following major surgical intervention (osteotomy),wound care with gauze impregnated with moxifloxacin hydrochloride gel(50 mg/ml). Wound closure with two button sutures. Check-up after 2days: slight wound pain, no postoperative oedema. Check-up after oneweek: removal of sutures, good wound margin adaptation, patientsymptom-free.

Patient C 5 (Male, 52 Years).

Clinical diagnosis: tooth 34, pulpitis purulenta, fistulation,submucosal swelling. Course of treatment: trepanation, incision,flushing of root canal and fistula with moxifloxacin hydrochloridesolution (50 mg/ml), canal insert with moxifloxacin hydrochloride gel(50 mg/ml), completion only with cotton wool plug, gauze insertimpregnated with moxifloxacin hydrochloride gel (50 mg/ml) in affectedregion, no suture. Check-up after 3 days: good healing process, patientsymptom-free. Root canal filling with endomethasone. Check-up after 3weeks: patient symptom-free.

Patient C 6 (Male, 44 Years).

Clinical diagnosis: tooth 36, wound care after extraction. Course oftreatment: dolor post, restoration of alveolus, application of depot ofmoxifloxacin hydrochloride gel (50 mg/ml) by gauze strips. Check-upafter 3 days: patient symptom-free, good wound margin adaptation.

Patient C 7 (Male, 36 Years).

Clinical diagnosis: tooth 22, wound care following root tip resectiondue to cyst. Course of treatment: incision, strip insert withmoxifloxacin hydrochloride gel (50 mg/ml). Check-up after 3 days:patient symptom-free, good healing process.

Patient C 8 (Female, 31 Years).

Clinical diagnosis: teeth 26 and 26 with apical granulomas, bitediscomfort. Course of treatment: extraction at inflammatory stage(osteotomy), wound care with gauze impregnated with grepafloxacin gel(50 mg/ml). Check-up after 3 days: patient is symptom-free.

Patient C 9 (Male, 22 Years).

Clinical diagnosis: tooth 14, pulpitis purulenta, fistulation,submucosal swelling. Course of treatment: trepanation, incision.Flushing of root canal and fistula with moxifloxacin hydrochloridesolution (25 mg/ml), canal insert with grepafloxacin gel (25 mg/ml),completion only with cotton wool plug. Gauze insert impregnated withmoxifloxacin hydrochloride gel (25 mg/ml) in affected region, no suture.Check-up after 6 days: patient symptom-free. Root canal filling withendomethasone. Check-up after 2 weeks: patient symptom-free.

D. Wound Care

Patient D 1 (Male, 33 Years).

Diagnosis: combustio escharotica on left forearm. Course of treatment:wound hygiene, application of moxifloxacin hydrochloride gel (1%), woundcovering. Regeneration of skin epithelium with complete wound closureafter one week.

Patient D 2 (Male, 25 Years).

Diagnosis: panaritium parunguale on right middle finger. Course oftreatment: conduction anaesthesia, opening at nail margin, localantibiosis with moxifloxacin hydrochloride gel (1%), insertion of rubberflap. Patient symptom-free.

Patient D 3 (Male, 70 Years).

Diagnosis: diabetes mellitus, hospital stay due to severe diabeticmicroangiopathy of the feet with diabetic foot syndrome. Then outpatientfoot care. Findings: a) deep, 2×1.5 cm ulcer under right big toe,greasy; b) large ulcer D III, 5 mm diameter; c) large fissure D IV/D V;severe keratinization of entire foot. Course of treatment: attemptedsystemic treatment with Avalox 400 and Clont 400 without significantchange in findings. Then application of dressings with moxifloxacinhydrochloride gel (1%) at weekly intervals. Wound check-up after 1stweek: a) ulcer D I, 1×0.5 cm, clean; b) ulcer D III clean; c) ulcer DIV/D V encrusted. Wound check-up after 2nd week: a) ulcer D Ipinhead-size, clean; b) ulcer D III, clean granular tissue; c) ulcer CIV/D V healed. Wound check-up after 3rd week: a) ulcer D I unchanged; b)ulcer D III pinhead-size. Wound check-up after 4th week: a) ulcer D Ihealed; b) ulcer D III healed.

Patient D 4 (Male, 62 Years).

Diagnosis: diabetes mellitus, diabetic microangiopathy of right footwith diabetic foot syndrome. Findings: 1×1 cm ulcer, greasy; severekeratinization of entire foot. Course of treatment: application ofdressings with moxifloxacin hydrochloride gel (1%) at weekly intervals.Wound check-up after 1st week: ulcer 0.2×0.4 cm, clean. Would check-upafter 2nd week: ulcer healed.

Patient D 5 (Female, 67 Years).

Diagnosis: diabetic gangrene on left big toe. Course of treatment: woundhygiene, removal of hyperkeratosis and necrosis. Four applications ofmoxifloxacin hydrochloride gel (1%) at weekly intervals, covering woundeach time. Regeneration of skin epithelium with complete wound closure,revascularization.

Patient D 6 (Male, 34 Years).

Diagnosis: erysipelas on right lower leg. Course of treatment:immobilization, local antibiosis with moxifloxacin hydrochloride gel(1%), local compresses. After 2 days, prevention of recurrence. Patientsymptom-free.

Patient D 7 (Female, 52 Years).

Diagnosis: phlegmons on palm of left hand. Course of treatment: incisionand wide opening of affected tissue areas, local antibiosis withmoxifloxacin hydrochloride gel (1%), wound care. After 2 days,repetition of local antibiosis. Patient symptom-free.

Patient D 8 (Female, 28 Years).

Diagnosis: furuncle on left forearm. Course of treatment: incision andopen wound treatment with moxifloxacin hydrochloride solution (1%).Patient symptom-free.

Patient D 9 (Female, 44 Years).

Diagnosis: carbuncle on back of neck. Course of treatment: excision ofall necrotic areas, open wound treatment with moxifloxacinhydrochloride-impregnated compress. Patient symptom-free.

1-29. (canceled)
 30. A method for the topical and/or local treatment ofwounds caused by infections comprising administering a therapeuticallyeffective amount of at least one compound of formula (I)

in which A is CH, CCl, CBr, C—CH₃, C—CN, C—OCH₃, C—OCHF₂ or N, R1 isC₁₋₅ alkyl, C₁₋₅ alkenyl, 2-fluoroethyl, cycloalkyl, bicycloalkyl,2-fluorocyclopropyl, 1-oxetan-3-yl, methylamino, optionally substitutedphenyl or pyridyl, or A and R1 together form the group—C—O—CH₂—CH(CH₃)—, R2 is hydrogen or C₁₋₃ alkyl, optionally substitutedby hydroxyl, halogen or amino, R3 is hydrogen, halogen, methyl, amino orNH—NH₂, R4 is hydrogen, halogen or amino, and R5 is an optionallymonosubstituted or polysubstituted mono-, bi- or tricyclic alicyclewhich is saturated or has at least one double bond and which optionallyhas at least one heteroatom in the ring system, or an aromatic mono-,bi- or tricycle optionally having at least one heteroatom, and/or atleast one compound of formula (II)

in which: R1 is hydrogen or C₁₋₃ alkyl, and R2 is an optionallymonosubstituted or polysubstituted mono-, bi- or tricyclic alicyclewhich is saturated or has at least one double bond and which optionallyhas at least one heteroatom in the ring system, or an aromatic mono-,bi- or tricycle optionally having at least one heteroatom, and/or theircorresponding hydrate and/or their corresponding physiologicallycompatible acid addition salt and/or optionally their correspondingphysiologically compatible salt of the carboxylic acid of the compoundsof general formula (I) in which R2 is H and/or the compounds of generalformula (II) in which R1 is H, and/or corresponding enantiomers and/orcorresponding diastereomers and/or corresponding racemates and/or acorresponding mixture of at least two of the above-mentioned compounds,and optionally other physiologically compatible auxiliary substances, toa subject in need thereof.
 31. The method of claim 30 where the wound iscaused by a postoperative or posttraumatic infection.
 32. The method ofclaim 31 where the wound is caused by a posttraumatic infectionresulting from cuts, stings, bruises, bites or gunshot wounds, infectedburns, hand infections, panaritium cutaneum, panaritium subcutaneum,panaritium ossale, panaritium articulare or tendovaginitis purulenta,postoperative sepsis, infected ulcers, gangrenes, mucosal ulcerations,acute bacterial skin infections, pyrodermia, erysipelas, furuncles,carbuncles, phlegmons, abscesses, ulcus cruris, infected decubitalulcers, blood blisters, erysipelas or erythrasma, and/or chronicbacterial skin infections, lupus vulgaris, swimming-pool granuloma,Buruli ulcers or actinomycosis, secondarily infected dermatoses, acne orrosacea.
 33. The method of claim 30 where in formula (I): A is CH, CCl,CBr, C—CH₃, C—CN, C—OCH₃, C—OCHF₂ or N, R1 is ethyl, 1,1-dimethyl-ethyl,1-ethenyl, 1,1-dimethyl-prop-2-ynyl, 2-fluoroethyl, cyclopropyl,bicyclo[1.1.1]pent-1-yl, 2-fluorocyclopropyl, 1-oxetan-3-yl,methylamino, 4-fluorophenyl, 2,4-difluorophenyl,5-amino-2,4-difluoro-phenyl, 5-fluoro-pyridin-2/1 or6-amino-3,5-difluoro-pyridin-2-yl, or A and R1 together form the groupC—O—CH₂—CH(CH₃)—, where the —CH(CH₃)-part of this group is bonded to thenitrogen atom of the heterocycle, R2 is hydrogen, methyl or ethyl, R3 ishydrogen, F, Cl, Br, methyl, amino or NH—NH₂, R4 is hydrogen, F oramino, R5 is optionally monosubstituted or polysubstituted cyclopropyl,azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl, morpholinyl, phenyl,pyrrolyl, pyridyl or imidazolyl, where at least two substituents areoptionally coupled together, and/or in formula (II), R1 is hydrogen, andR2 is optionally monosubstituted or polysubstituted cyclopropyl,azetidinyl, pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl, whereat least two substituents are optionally coupled together.
 34. Themethod of claim 30 where in formula (I): A is CH, CCl, C—CN, C—OCH₃ orN, R1 is cyclopropyl, 2-fluorocyclopropyl, 4-fluorophenyl or2,4-difluorophenyl, or A and R1 together form the groupC—O—CH₂—CH(CH₃)—, where the —CH(CH₃)-part of this group is bonded to thenitrogen atom of the heterocycle, R2 is hydrogen, R3 is hydrogen oramino, R4 is hydrogen or F, R5 is optionally monosubstituted orpolysubstituted pyrrolidinyl, piperidinyl, piperazinyl or morpholinyl,where at least two substituents are optionally coupled together.
 35. Themethod of claim 30 where in formula (I): A is CH, CCl, C—OCH₃ or N, R1is cyclopropyl or 2,4-difluorophenyl, or A and R1 together form thegroup C—O—CH₂—CH(CH₃)—, where the —CH(CH₃)—part of this group is bondedto the nitrogen atom of the heterocycle, R2 is hydrogen, R3 is hydrogenor amino, R4 is hydrogen or F, and R5 is pyrrolidinyl, piperidinyl,piperazinyl, morpholinyl or 3-aza-bicyclo[3.1.0]hexyl optionallysubstituted by amino, methyl, aminomethyl and/or methoxyimino, orpiperidino-pyrrolidinyl.
 36. The method of claim 30 where in formula(II): R1 is hydrogen, and R2 is optionally monosubstituted orpolysubstituted cyclopropyl, azetidinyl, pyrrolidinyl, piperidinyl,piperazinyl or morpholinyl, where at least two substituents areoptionally coupled together.
 37. The method of claim 30 where thecompound is selected from at least one of1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-743-(methylamino)-1-piperidinyl]-4-oxo-3-quinolinecarboxylicacid (balofloxacin),8-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-7-[(4aS,7aS)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]-4-oxo-3-quinolinecarboxylicacid monohydrochloride (BAY Y3118),1-cyclopropyl-6-fluoro-8-difluoromethoxy-1,4-dihydro-7-((3S)-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylicacid hydrochloride (caderofloxacin),1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylicacid (ciprofloxacin),7-(3-amino-1-pyrrolidinyl)-8-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid (clinafloxacin),(1a,5a,6b)-(+)-7-(6-amino-1-methyl-3-azabicyclo[3.2.0]hept-3-yl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylicacid (ecenofloxacin),1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-1,8-naphthyridine-3-carboxylicacid (enoxacin),1-cyclopropyl-7-(4-ethyl-1-piperazinyl)-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid (enrofloxacin),6-fluoro-1-(5-fluoro-2-pyridinyl)-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylicacid (fandofloxacin),1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(3-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylicacid (gatifloxacin),7-[(4Z)-3-(aminomethyl)-4-(methoxyimino)-1-pyrrolidinyl]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylicacid (gemifloxacin),1-cyclopropyl-6-fluoro-1,4-dihydro-5-methyl-7-(3-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylicacid (grepafloxacin),(3S)-9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylicacid (levofloxacin),1-cyclopropyl-8-fluoro-1,4-dihydro-8-methoxy-74(40S,70S)-octahydro-6H-pyrrolo[3,4-b]pyridin-6-y11-4-oxo-3-quinolinecarboxylicacid (moxifloxacin),9-fluoro-6,7-dihydro-8-(4-hydroxy-1-piperidinyl)-5-methyl-1-oxo-1H,5H-benzo[ij]quinolizine-2-carboxylicacid (nadifloxacin),1-ethyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-3-quinolinecarboxylicacid (norfloxacin),9-fluoro-2,3-dihydro-3-methyl-10-(4-methyl-1-piperazinyl)-7-oxo-7H-pyrido[1,2,3-de]-1,4-benzoxazine-6-carboxylicacid (ofloxacin),5-amino-7-[(7S)-7-amino-5-azaspiro[2.4]hept-5-yl]-1-cyclopropyl-6-fluoro-1,4-dihydro-8-methyl-4-oxo-3-quinolinecarboxylicacid (olamufloxacin),(3S)-10-(1-aminocyclopropyl)-9-fluoro-2,3-dihydro-3-methyl-7-oxo-7H-pyrido[1,2,3-de]1,4-benzoxazine-6-carboxylicacid (pazufloxacin),1-ethyl-6-fluoro-1,4-dihydro-7-(4-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylicacid (pefloxacin),6-fluoro-1-methyl-744-[(5-methyl-2-oxo-1,3-dioxot-4-yOmethyl]-1-piperazinyll-4-oxo-1H,4H41,3]thiazeto[3,2-a]guinoline-3-carboxylicacid (prulifloxacin),1-ethyl-1,4-dihydro-4-oxo-7-(4-pyridinyl)-3-quinolinecarboxylic acid(rosoxacin), 7-[(7S)-7-amino-5-azaspiro[2.4]hept-5-yl]-8-chloro-6-fluoro-1-[(1R,2S)-2-fluorocyclopropyl)-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid (sitafloxacin),7-(3-amino-1-pyrrolidinyl)-1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylicacid (tosufloxacin), and7-(1a,5a,60-6-amino-3-azabicyclo[3.1.0]hex-3-yl)-1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylicacid (trovafloxacin),
 38. The method of claim 37 where the compound isselected from at least one of7-(3-amino-1-pyrrolidinyl)-8-chloro-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylicacid (clinafloxacin),1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(3-methyl-1-piperazinylY4-oxo-3-quinolinecarboxylicacid (gatifloxacin),7-[(4Z)-3-(aminomethyl)-4-(methoxylmino)-1-pyrrolidinyl]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylicacid (gemifloxacin),1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-[(4aS,7aS)octahydro-6H-pyrrolo[3,4-b]pyridin-6-yl]-4-oxo-3-quinolinecarboxylicacid (moxifloxacin),7-(3-amino-1-pyrrolidinyl)-1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylicacid (tosufloxacin), and7-(1a,5a,6a-6-amino-3-azabicyclo[3.1.0]hex-3-yl)-1-(2,4-difluorophenyl)-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylicacid (trovafloxacin).
 39. The method according to claim 37 where thecompound is selected from at least one of1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-(3-methyl-1-piperazinyl)-4-oxo-3-quinolinecarboxylicacid (gatifloxacin),7-[(4Z)-3-(aminomethyl)-4-(methoxyimino)-1-pyrrolidinyl]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylicacid (gemifloxacin) and1-cyclopropyl-6-fluoro-1,4-dihydro-8-methoxy-7-[(4aS,7aS)-octahydro-6H-pyrrolop,4-bipyridin-6-y11-4-oxo-3-quinolinecarboxylicacid (moxifloxacin).
 40. The method of claim 30 where the acid additionsalts are selected from the group consisting of hydrochloride,hydrobromide, methanesulfonate and tolylsulfonate.
 41. The method ofclaim 30 where the physiologically compatible salts of the carboxylicacid are selected from the group consisting of alkali metal salts,alkaline earth metal salts, ammonium salts, silver salts and guanidiniumsalts.
 42. The method of claim 30 wherein the wound is present in ahuman or an animal.
 43. A gelatinous formulation containing at least onecompound of formula (I)

in which A is CH, CCl, CBr, C—CH₃, C—CN, C—OCH₃, C—OCHF₂ or N, R1 isC₁₋₅ alkyl, C₁₋₅ alkenyl, 2-fluoroethyl, cycloalkyl, bicycloalkyl,2-fluorocyclopropyl, 1-oxetan-3-yl, methylamino, optionally substitutedphenyl or pyridyl, or A and R1 together form the group—C—O—CH₂—CH(CH₃)—, R2 is hydrogen or C₁₋₃ alkyl optionally substitutedby hydroxyl, halogen or amino, R3 is hydrogen, halogen, methyl, amino orNH—NH₂, R4 is hydrogen, halogen or amino, and R5 is an optionallymonosubstituted or polysubstituted mono-, bi- or tricyclic alicyclewhich is saturated or has at least one double bond and which optionallyhas at least one heteroatom in the ring system, or an aromatic mono-,bi- or tricycle optionally having at least one heteroatom, and/or atleast one compound of formula (II)

in which: R1 is hydrogen or C₁₋₃ alkyl, and R2 is an optionallymonosubstituted or polysubstituted mono-, bi- or tricyclic alicyclewhich is saturated or has at least one double bond and which optionallyhas at least one heteroatom in the ring system, or an aromatic mono-,bi- or tricycle optionally having at least one heteroatom, and/or theircorresponding hydrate and/or their corresponding physiologicallycompatible acid addition salt and/or optionally their correspondingphysiologically compatible salt of the carboxylic acid on which it isbased, i.e. compounds of formula (I) in which R2 is H and/or thecompounds of formula (II) in which R1 is H, and/or correspondingenantiomers and/or corresponding diastereomers and/or correspondingracemates and/or a corresponding mixture of at least two of theabove-mentioned compounds, and optionally other physiologicallycompatible auxiliary substances, wherein the compounds of formula (I)and/or of formula (II) are present in concentrations of from 0.005 mg/mlto 200 mg/ml.
 44. The gelatinous formulation of claim 43 which containsas physiologically compatible auxiliary substances, solvents, gellingagents, surface-active compounds, thickeners or mixtures of at least twoof these auxiliary substances.
 45. The gelatinous formulation of claim44 which contains modified celluloses, polyalkylene glycols and waterand optionally at least one polysorbate.
 46. The gelatinous formulationof claim 45 which contains, as the polysorbate, at least one mono-, di-or triester of oleic acid, lauric acid, palmitic acid or stearic acidand sorbitol and/or its anhydride with up to 20 mol of ethylene oxideunits per mol of sorbitol or anhydride.
 47. The gelatinous formulationof claim 43 which has been applied to an inert carrier or an inertcarrier material or has been incorporated therein.
 48. The gelatinousformulation of claim 47 where the inert carriers are strip inserts,thread inserts, chips, trays, collagen sponges, tampons, cotton woolplugs or foam pellets.
 49. The gelatinous formulation according to claim43 where the compounds of formula (I) and/or of formula (II) areemployed in concentrations of from 0.5 mg/ml to 200 mg/ml.
 50. Thegelatinous formulation according to claim 49 where the compounds offormula (I) and/or of formula (II) are employed in concentrations offrom 10 mg/ml to 150 mg/ml.
 51. The method of claim 30 where thecompounds of formula (I) and/or of formula (II) is administered in theform of a solution, a suspension, an emulsion, in form of liposomes orin form of micelles and has optionally been applied to or incorporatedin a carrier material or an inert carrier according to claim
 19. 52. Themethod of claim 51 where the compounds of formula (I) and/or of formula(II) are administered in the form of an aqueous solution.
 53. The methodaccording to claim 22 where the compounds of formula (I) and/or offormula (II) are administered in the form of a medicament whichcontains, as other physiologically compatible auxiliary substances,solvents, solubilizers, thickeners, preservatives, emulsifiers, mucins,osmolality regulators, antioxidants, chelating agents, disinfectants,dispersants, emulsion stabilizers, hydrocolloids, wetting agents or amixture of at least two of the above-mentioned auxiliary substances.